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Keibel F. The Development of the Sense Organs. (1912) chapter 16, vol. 2, in Keibel F. and Mall FP. Manual of Human Embryology II. (1912) J. B. Lippincott Company, Philadelphia.

XVI. The Development of the Sense Organs: General Considerations | Touch Cells | Epibranchial Sense Organs | Gustatory Organ | Olfactory Organ | Eye | Ear | Manual of Human Embryology II
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This 1912 chapter by Keibel describes sensory development within the human (and other) embryos. Note that Keibel was the two volume textbook co-editor and also the editor of the series Normal Plates of the Development of Vertebrates.

Links below are to the modern sensory notes, that also include links to other historic sensory development articles.

Senses Links: Introduction | placode | Hearing and Balance hearing | balance | vision | smell | taste | touch | Stage 22 | Category:Sensory

Hearing Links: Introduction | inner ear | middle ear | outer ear | balance | placode | hearing neural | Science Lecture | Lecture Movie | Medicine Lecture | Stage 22 | hearing abnormalities | hearing test | sensory | Student project

  Categories: Hearing | Outer Ear | Middle Ear | Inner Ear | Balance

Historic Embryology - Hearing 
Historic Embryology: 1880 Platypus cochlea | 1892 Vertebrate Ear | 1902 Development of Hearing | 1906 Membranous Labyrinth | 1910 Auditory Nerve | 1913 Tectorial Membrane | 1918 Human Embryo Otic Capsule | 1918 Cochlea | 1918 Grays Anatomy | 1922 Human Auricle | 1922 Otic Primordia | 1931 Internal Ear Scalae | 1932 Otic Capsule 1 | 1933 Otic Capsule 2 | 1936 Otic Capsule 3 | 1933 Endolymphatic Sac | 1934 Otic Vesicle | 1934 Membranous Labyrinth | 1934 External Ear | 1938 Stapes - 7 to 21 weeks | 1938 Stapes - Term to Adult | 1940 Stapes | 1942 Stapes - Embryo 6.7 to 50 mm | 1943 Stapes - Fetus 75 to 150 mm | 1946 Aquaductus cochleae and periotic (perilymphatic) duct | 1946 aquaeductus cochleae | 1948 Fissula ante fenestram | 1948 Stapes - Fetus 160 mm to term | 1959 Auditory Ossicles | 1963 Human Otocyst | Historic Disclaimer

Vision Links: vision | lens | retina | placode | extraocular muscle | cornea | eyelid | lacrima gland | vision abnormalities | Student project 1 | Student project 2 | Category:Vision | sensory
Historic Embryology - Vision 
Historic Embryology: 1906 Eye Embryology | 1907 Development Atlas | 1912 Eye Development | 1912 Nasolacrimal Duct | 1917 Extraocular Muscle | 1918 Grays Anatomy | 1921 Eye Development | 1922 Optic Primordia | 1925 Eyeball and optic nerve | 1925 Iris | 1927 Oculomotor | 1928 Human Retina | 1928 Retina | 1928 Hyaloid Canal | Historic Disclaimer

Smell Links: Introduction | placode | Rhinencephalon | head | respiratory | Student project | taste | sensory | Category:Smell
Historic Embryology - Smell 
Historic Embryology: 1902 Olfactory Structures | 1910 cavum nasi | 1940 Olfactory and Accessory Olfactory Formations | 1941 Olfactory nerve | 1944 Jacobson’s organ | 1980 Staged embryos

Taste Links: Introduction | Student project | Tongue Development | Category:Taste
Historic Taste 
Historic Embryology: 1888 human infant papilla foliata | 1889 man taste-organs | Paper - Further observations on the development of the taste-organs of man|1889 further man taste-organs]]
Historic Disclaimer - information about historic embryology pages 
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Pages where the terms "Historic" (textbooks, papers, people, recommendations) appear on this site, and sections within pages where this disclaimer appears, indicate that the content and scientific understanding are specific to the time of publication. This means that while some scientific descriptions are still accurate, the terminology and interpretation of the developmental mechanisms reflect the understanding at the time of original publication and those of the preceding periods, these terms, interpretations and recommendations may not reflect our current scientific understanding.     (More? Embryology History | Historic Embryology Papers)

Development Of The Eye

Franz Keibel
Franz Keibel (1861 - 1929)

The eyes of vertebrates differ from those of all other animals, with the exception of the ascidians, in that their apparatus for receiving the light stimuli has its origin from the anlage of the central nervous system, while in other animals, as would seem to be the natural way, it arises from the epidermis. Consequently the eyes of the vertebrates are all constructed upon the same plan, a plan which occurs only here and there among invertebrates (in the edge of the mantle of the lamellibranchs Pecten and Spondylus and on the back of the pulmonate mollusk Onchidium). Among the invertebrates the eyes vary greatly in structure, decided differences occurring in members of the same class, indeed even in closely related species. Attempts to derive the eyes of vertebrates from those of invertebrates have not been lacking, but in my opinion these have so far been unsuccessful.[1] To these vain attempts I would also add that of Boveri (1904) who would derive the vertebrate eye from the optic cells of Hesse in Amphioxus.

Much more readily can a relationship of the vertebrate eye to those of the ascidians be imagined; indeed, Froriep (1906) has recently shown that it is probable that the ascidian eye is not to be regarded as an unpaired structure, but is the right member of a pair, its fellow of the left side having degenerated. Also both the vertebrate and ascidian eyes are cerebral eyes. However, even on this point, one must accept the cautious statement of Froriep, who maintains that there can be no question of the phylogenetic derivation of the vertebrate eye from that of the ascidian larva by direct descent, although both organs have come from an identical type, which the optic pits of the vertebrate embryo resemble more closely than does the eye of the ascidian larva.

Fig. 158. (From the Normentafel of Keibel and Elze, Fig. 6b.) A., anlage of the eye; Hpl., auditory plate; 1 Kt., first branchial pouch; N., neuromere. X 15.

The attempt of Brachet (1907, 1 1907 2 ) to derive the eye, and especially the lens, from an epibranchial sense organ, a placode, has already (p. 182) been mentioned.

Fig. 159. Section through an optic pit of Fig. 158 more highly magnified. (After Low, 190S, p. 247, Fig. 13.) A., anlage of the eye; Ep., anlage of the epidermis; VH., forebrain.

Preparatory to a detailed consideration of the development of the human eye I shall give a synopsis of the process.

The first anlage of the eye of vertebrates and of man appears in the most anterior portion of the still open anlage of the brain as the optic pits, foveolae opticse. Fig. 158 shows these pits as they are seen in section from a human embryo of 2.6 mm., with 13 or 14 pairs of primitive somites (compare Plate 6 of the Normentafel of Keibel and Elze), and in Fig. 159 there is shown under a higher magnification a neighboring section of one of the pits. The pits are here fairly well developed, and there can be no doubt that they are also recognizable in man in the yet widely open medullary tube, at a stage corresponding with that shown in the model prepared from one of Keibel's pig embryos (Fig. 160). If the medullary tube be supposed to close, the pits would be converted into the optic vesicles. These are broad evaginations of the most anterior part of the brain anlage, the ventricular cavity of the brain being prolonged into them to form their cavities, so that one may very well speak of the optic ventricles. Later the anlagen of the optic vesicles become more sharply separated from the anlage of the forebrain and acquire stalks, the optic stalks (pediculi optici), as may be seen from Fig. 161. A transverse section through an optic vesicle before the stalk is distinctly developed is shown on the left side of Fig. 162. The section is taken from an embryo of 4 mm (compare Plate 10 of the Normentafel of Keibel and Elze).

Keibel Mall 2 160.jpg

Fig. 160. Rostrolateral view of the head of a pig embryo (Sus scrofa) of 4.7 mm, with 10 primitive somites and 16 days old. Drawn from a model by F. Keibel (1897). (After Froriep (1905), in Hertwig'e Handbuch, vol. Us, p. 156, Fig. 159.) X ca. 25.

Sections through distinctly stalked vesicles are shown in Figs. 163 and 164; they are taken from the embryos of 4.9 and 4 mm of Plates 14 and 13 of the Normentafel, the larger one (Plate 14) having 35 and the smaller (Plate 13) 34 pairs of primitive somites; the optic vesicles of the larger embryo are, however, less developed than those of the smaller one ; Fig. 164 especially shows the transition of the optic vesicle to the optic cup, which must now be considered.

The optic cup, cupula optica or vesicula optica inversa, is formed from the optic vesicle by its distal wall becoming thickened and its distal and ventral portions invaginating toward the proximal layer. The invagination extends for some distance along the stalk of the optic vesicle, which has now become the stalk of the optic cup, pediculus cupulas opticas. Such an optic cup is shown connected with the brain in Fig. 165, drawn from a model by His.

During the transformation of the optic vesicle into the optic cup some other processes of importance for the development of the eye have begun. The epithelium over the proximal part of the optic vesicle at first thickens (already indicated in the stage shown in Fig. 162), then becomes differentiated from the surrounding tissues as the lens plate, and finally becomes depressed to form the lens pit. These stages are shown in Figs. 166 a and b and 167 a, b, and c. The lens pit then closes to form the lens vesicle, as is shown in Fig. 168 a and b. P'ig. 169 is from an embryo of about the same stage as that of Fig. 168 and is shown under greater magnification; it is from an embryo of Hochstetter's collection (compare the Normentafel of Keibel and Elze, Plate 28 and the figure xiii; also Elze, 1907). In the outer layer of the anlage of the retina traces of pigment are to be seen, and the lens vesicle has just closed, the point of closure being still recognizable. The inner, distal wall of the optic cup is greatly thickened. In the interior of the lens vesicle, in addition to scattered degenerating cells, there is a mass of cells resting on the proximal wall. From the lens vesicle, in a manner to be fully described later, the lens and the lens capsule are formed. The distal layer of the optic cup may from its mode of origin be termed the lamina inversa cupula or from its later fate the retinal layer, and at first the lens lies close upon it, so that it almost or completely fills the cavity of the cup, the antrum cupulae, but later the retinal layer of the optic cup and the proximal layer of the lens gradually separate from each other. In this way is formed the cavity for the vitreous humor, cavum hyaloideum oculi, in which the vitreous humor, corpus vitreum, is formed in a manner that will be described later.

Keibel Mall 2 161.jpg

Keibel Mall 2 162.jpg

Fig. 161. (After His, 1889, from Froriep in Hertwig's Handbuch, vol. II2, p. 183, Fig. 187.) Xca. 50. au, opiio vesicle; e, telencephalon; m, mesencephalon; z, diencephalon. Fig. 162. (From the Normentafel of Keibel and Elze, Fig. 9d.) X 30. The right optic vesicle (the left in the figure) is in wide connection with the ventricle of the forebrain, the stalk of the left vesicle (the right in the figure) is cut tangentially. A., optic vesicle; SA.b., second branchial arch artery; Hy., hypophysis; lKt., first branchial pouch; iV.ffZ., glossopharyngeal nerve; N.v., vagus nerve;, branchial sense-organ on the glossopharyngeal nerve.

Keibel Mall 2 163.jpg

Keibel Mall 2 164.jpg

Fig. 163. Section through the anterior part of the head of a human embryo of 4.9 mm. (From the Normentafel of Keibel and Elze, Fig. 12h.) X30. A., anlageof the optic cup; L., anlage of the lens. Fig. 164. Section through the anterior part of the head of a human embryo of 4 mm. (From tha Normentafel of Keibel and Elze, Fig. llf.) X30. A., anlage of the optic cup; L., anlage of the lens.

Keibel Mall 2 165.jpg

Fig. 165. Mesencephalon and telencephalon of a human embryo from the end of the fourth week, seen from the right side and from below. Prepared from His's wax model by Fr. Ziegler. (From Froriep (1905), in Hertwig's Handbuch, vol. II2, p. 184, Fig. 18S.) Xca. 37. he, cerebral vesicle; in, infundibulum; ma, mammillary process; mi, mesencephalon; op, torus opticus; t, lamina ferminalis; zw, diencephalon.

Keibel Mall 2 166.jpg

Fig. 166 a and b. a: Section through the anterior part of the head and through the heart region of a human embryo of 5 mm. X 25. b: Section through the anlage of an eye of the same embryo. X 100. (After drawings by Hammar, from the Normentafel of Keibel and Elze.) F., thread-like tissue between the lens and the anlage of the retina; Oe., oesophagus; SI, septum I (Born); S.sp., septum spurium (His); Tr.a., truncus arteriosus; Uk., lower jaw; Z., cell mass in the lens pit.

Keibel Mall 2 167.jpg

Fig. 167 a, b, and c. a and b: Sections through the right optic cup and the pit-like anlage of the lens with its epithelial growth; mesenchyme cells occur between the distal layer of the optic cup and the anlage of the lens, c: A corresponding section through the anlage of the left eye. X 50. (From tbe Normentafel of Keibel and Elze.)

Keibel Mall 2 168.jpg

Keibel Mall 2 169.jpg

Fig. 168 a and b. a: Section through the anterior part of the head of a human embryo of 6.25 mm, passing through the optic cup and the lens vesicle which is being constricted off from the epidermis. In the interior of the lens vesicle there is a mass of degenerated cells, shown more distinctly in Fig. b. a X20; b X50.

(From the Normentafel of Keibel and Elze, Fig. I8 b and d.)

Fig. 169. Section through the optic anlage of an embryo of 7 mm. From a drawing kindly furnished me by Professor Hochstetter of Vienna. X 100. For explanation see text.

Figs. 170, 171, and 172 will serve to complete the description so far as it has been given. I am indebted to Professor Hochstetter for them; they have been drawn from models prepared by F. Dedekind of Innsbruck under Hochstetter's direction. Figs. 170 and 171 are from models that have been divided into an anterior and a posterior part in the line of the chorioidal fissure; one looks from behind on the apical half of the right eye. The model represented in Fig. 170 is from the embryo Braus (greatest length = nape length, 6.3 mm.), which Hochstetter has figured in his " Bildern der ausseren Korperform einiger menschlicher Embryonen" (Munich, 1908), and also in the sixth chapter of the Handbuch as Fig. 47 (p. 77). The stalk of the optic cup is short and broad. The lens pit is still open and for the most part lies close upon the distal layer of the cup; a blood-vessel, the hyaloid artery, is beginning to penetrate between the distal layer of the optic cup, which is the anlage of the retina, and the Lens. The embryo from which the model represented in Fig. 171 was prepared was Embryo Chr. 1 of Hochstetter's collection. It has been figured by Hochstetter (I.e.) and by Keibel and Elze in the Normentafel, Fig. XIII (compare Plate 28 of the Normentafel) ; Fig. 169 shows a section through the optic anlage of the same embryo, which has been thoroughly studied by Elze (1907). The stalk of the optic cup has become somewhat longer and narrower, and the distal layer of the cup is decidedly more thickened. The lens has just closed and is still connected with the epidermis. The space for the vitreous body, between the distal layer of the optic cup (anlage of the retina) and the lens, has become somewhat broader and the hyaloid artery shows the formation of an island. Fig. 172 shows the optic cup of an embryo of 12.5 mm. seen from the side and from below; one looks directly into the chorioid fissure and through the proximal region of this into the cavity for the vitreous body. The chorioid fissure is almost closed; it is narrowest at its middle. Distally one sees the lens surrounded by the border of the optic cup. The degree of development of the organs of the embryo (Ma 1 of Hochstetter's collection) from which this model was prepared is shown in the Normentafel of Keibel and Elze in Plate 56.

Keibel Mall 2 170.jpg

Keibel Mall 2 171.jpg

Fig. 170. Apical half of one of the optic anlagen of an embryo of 6.3 mm greatest length (nape-length), seen from behind. After one of Hochstetter's models prepared by F. Dedekind of Innsbruck. X 100. For explanation see text. Fig. 171. Apical half of one of the optic anlagen of an embryo of 7 mm, seen from behind. After one of Hochstetter's models prepared by F. Dedekind of Innsbruck. X 100. For explanation see text.

Keibel Mall 2 172.jpg

Fig. 172. Optic anlage of an embryo of 12.5 mm seen from the side and from below. From one of Hochstetter's models prepared by F. Dedekind of Innsbruck. X 100. For explanation see text.

We may now, in the first place, take up the development of the lens. After it has separated from the epidermis its anlage lies at first close to the layer that gave origin to it, but later the two structures become separated by mesoderm, mesenchymatous cells growing in between them (Fig. 173). In these cells is formed the anterior chamber of the eye; the larger distal portion of the cells becomes the substantia propria of the cornea, together with Descemet's membrane and the endothelium of the chamber, the much smaller proximal portion gives rise to the portion of the capsula vasculosa lentis which has long been known as the pupillary membrane and which degenerates before birth. The mesodermal tissue that surrounds the optic cup is continuous with the anlage of the cornea, and from it there are formed the chorioid, corpus ciliare, iris, and sclera. While these structures, whose development will be followed in detail later on, are forming, import ant changes take place in the region of the optic cup and of its stalk. In its thin proximal layer, the lamina externa cupnlsB, pigment is deposited and it becomes the pigment layer of the retina.

The distal layer, the lamina inversa cupulae, or, as it has already been named, the retinal layer, undergoes further differentiation. As far forward as the ora serrata it becomes the actual retina; distal to that it thins to become the pars caeca or the regio cilioiridica, which, as its name indicates, is again separable into a pars ciliata and a pars iridica.

It may be mentioned here that the musculus sphincter and the musculus dilatator pupillas are formed from the pigment layer of the cupula optica in the iris region. The chorioid fissure, fissura cupulae, which is formed by the optic vesicle invaginating not directly distally, but ventrally and distally, becomes closed, and thus the bulbus oculi is formed. It is connected with the brain by the optic nerve, into which the stalk of the optic cup becomes transformed.

Keibel Mall 2 173.jpg

Fig. 173. Section through the optic anlage of a human embryo of 11 mm (Embryo Pi of Hochstetter's collection; the embryo is figured in Hochstetter's series of figures, in the Normentafel of Keibe and Elze, where a statement of the degree of development of its organs is given, and on p. 74, Fig. 52, of this Handbook.) The pigment, which is abundantly deposited in the outer layer of the optic cup and which extends almost into the optic stalk, does not show under the magnification (X 100) employed. The thickened proximal wall of the lens vesicle fills about the half of the lumen of this structure, and in the lumen are degenerating cells. X 100.

Later the lids are formed as protective and accessory apparatus ; they are folds of skin which grow over the anlagen of the eye from above and below, and, for a time, they fuse together completely, so that the bulbus oculi is completely closed off from the outer world. By the formation of the lids the conjunctival sac is formed, and from this the lachrymal glands are developed, while the lachrymal sac and the lachrymo-nasal duct are connected with it by the lachrymal canals. Mention may also be made of the development of the third eyelid, the plica semilunaris, the caruncula lacrimalis, and the eye muscles.

Now that a general idea of the development of the eye and its accessory apparatus has been obtained, we may return to the first developmental processes and consider for a little the optic pits. Their early appearance in the still open medullary tube has already been mentioned; thus during their earliest formation the light perceiving organs lie at the surface, and in this stage the part of the retina which corresponds to the rods and cones, the receptors for the light stimulus, is turned towards the light. It has been stated in the introduction to this section that it is in this stage that Froriep (1906) finds the primitive form common to the eyes of vertebrates and ascidians. It is noteworthy that in this stage the optic pits lie immediately in contact with the ectoderm, no mesodermal cells intervening, but the mesoderm seems to have penetrated further in a slightly older stage, a section of which has been figured by Bryce (1908). Low (1908, p. 248) concludes that the cells of the wall of the pit must be arranged in several rows, since the nuclei are arranged on several levels, but from the situation of the mitoses I hold them to be arranged in a single layer, the nuclei alone being in several.

It may be noted here that the anlagen of the optic pits in the Amphibia are present in posse before they are visible. This is shown by the experiments of W. H. Lewis (1906) and Spemann (1906) ; portions of the medullary plate corresponding in position with the optic pits if removed and implanted elsewhere give rise to optic vesicles.

On the closure of the medullary tube the optic pits become transformed into the optic vesicles.

As to the correctness of the description of the development of the optic vesicle given here there can be no doubt; yet I may point out that another view would still seem to persist. In the first place, Druault, following Dareste, gives it in Poirier's Traite d'anatomie humaine (vol. 5, p. 1007) and Van Duyse (1904) also adheres to it. According to this view the anlage of the optic vesicle lies originally in the ectoderm covering the anlage of the head and only wanders into the anlage of the brain during the closure of the medullary tube. This hypothesis clearly owes its origin to the apparent absurdity involved in the origin of an organ for the reception of light stimuli in the interior of the body. That the hypothesis is false is shown by direct observations in man and in many animals arid, in addition, by the experiments that have just been cited.

The optic vesicles are at first in wide communication with the ventricles of the fore-brain, but gradually they become stalked, the stalk, however, when it is developed, not being attached to the middle of the vesicle, but somewhat ventrally, as is shown in Fig. 161. As is shown in the embryo from which Fig. 162 is taken, the proximal wall of the optic cup becomes somewhat thickened at an early stage, but it must be composed of a single layer of cells in this stage and also later, as is shown by the mitoses ; the nuclei, however, are in several layers. Mesoderm lias already become interposed in quantity between the distal wall of the cup and the ectoderm, but it disappears again later either completely or with the exception of very slight traces. This is shown on Plates 7, 8, 9. 10, 11, 13, 14, 17. IS, 19. and 20 of the Normentafel of Keibel and Elze (1908). The conditions in the human embryo are apparently the same as those that I observed (1895, 1897) in a very complete series of pig embryos.

By the distal wall of the vesicle becoming thickened and invaginating toward the proximal and upper wall, the vesicle is transformed into the optic cup. The idea that formerly obtained, that the invagination and the transformation of the vesicle into the cup was due to the anlage of the lens, must be given up, for the thorough study of the normal process of development speaks against such a view, as do also occasional malformations (Eabl, I s '. »S) and, especially, the results of experimental investigations i W. H. Lewis, 1904, Spemann. 1901) ; these last show that anlagen of optic vesicles, implanted in abnormal situations, will become transformed into optic cups without any formation of a lens. Such experiments have shown that in certain amphibia not only is the stimulus supplied by the distal wall of the optic vesicle to the ectoderm lying over it necessary for the formation of a lens, but also that the stimulus arouses the ectoderm to lens formation not only in the region where this takes place in normal development, but also elsewhere. In this connection importance is to be attached to the fact that in mammalia, and also in man, the contact of the distal wall of the optic vesicle with the ectoderm lying above it is reestablished at the time of formation of the lens. Froriep (1905 1 ) has endeavored to determine the exact method by which the transformation of the vesicle into the cup is brought about. He comes to the conclusion that it is produced not so much by an invagination of the floor of the cup as by an outgrowth of its margin. According to this view, the pupillary opening (os pupillare cupula) and chorioid fissure of the cup are gaps persisting between the outgrowing walls. But when Froriep states that the motive for this formation of the cup and the chorioid fissure is "that the apparatus for the reception of light may keep open the shortest path to the central organ, " he is merely offering a restatement of the facts rather than an explanation of them. The chorioid fissure, by which vessels for the vitreous body pass into the cavity of the cup. closes later on, and there then remains only the pupillary opening of the cup and the opening where the arteria centralis retina penetrates the optic nerve, at the point where the fissure originally faded out upon the optic stalk.

According to Szily (1907), who bases his conclusion on models prepared from human embryos as well as on others from higher vertebrates, the closure of the chorioid fissure takes place first at about the middle of its length and thence proceeds in both the proximal and the distal direction. Zumstein and Osaki. (1901 ! and 1902 2 ), who also worked by the wax-plate method, found that it closes from the distal toward the proximal end ('from before backwards"), and Keil (1906) found the same thing in the case of the pig. Minot (1894) found just the reverse; according to his observations, the closure takes place first at the proximal end. Further observations seem necessary to settle this point ; perhaps it is a case of variable conditions.

The fetal chorioid fissure explains a number of forms of coloboma as inhibition phenomena, since, if it does not close, the development of the chorioid, the corpus ciliare, and the iris is also inhibited in the region of the persistent fissure. But all colobomata are not inhibition formations. In order to bring them all into this one category arbitrary rotations of the optic cup have been assumed; yet even these movements of the optic vesicle and cup do not suffice to explain all the cases. (See also H. Virchow, 1901, and Hippel, 1903.) The optic anlagen during their development undergo some more or less important changes of position, among which may be recognized certain ones that are associated with changes in the anlagen of the brain ; these changes are more especially correlated with the vertex bend of the brain and need not be further considered here. In addition there are also changes which may be regarded as peculiar to the optic anlagen, although they also may be induced by the connection of the anlagen with the brain. At first the eyes are directed laterally, but with the development of the face they move medially — and this is especially marked in man — so that the optic axes make with one another a gradually diminishing angle. According to Kollmann (1898), the angle in the sixth week of development is 90°. Dedekind (1909) finds that the optic nerve of an embryo of 19 mm. vertex-breech length and 12 mm. head length forms an angle with the median plane of about 65°, while in the fully developed condition this angle is decidedly less, only about 38° or 40°. In addition to this change of position several authors have described a rotation of the anlage of the bulb around its long axis. Vossius (1883) has placed the amount of this rotation at about 90°, basing his estimate on the facts, first, that the point of entrance of the blood-vessels into the optic nerve is at first below and in the median line, whereas in the adult individual it is situated more laterally; secondly, that the m. rectus superior comes to lie beneath the m. levator palpebral superioris, although it is originally lateral to it; and. thirdly, that the bundles of nerve-fibres in the optic nerve pursue a spiral course.

Devi (1896) has shown that the conclusions of Vossius are not tenable. The investigations of Strahl (1898) and Henckel (1898) have shown that Devi's criticisms of the results of Vossius were entirely justified, but they also showed that in younger stages than had been studied by Vossius and Deyl — that is to say, before the third month — a rotation through about 45° occurred. Originally the fissure in the distal portion of the optic nerve lies in the lower inner quadrant, but later the point of entrance of the a. centralis retinae is situated exactly or almost exactly in the under surface. After the third month no further alteration in the position of the point of entrance of this artery can be observed. A movement of the m. levator palpebrae superioris over the medial border of the m. rectus superior does, it is true, take place to a certain extent, but it has nothing to do with a rotation of the bulb. Even the rotation in the earliest stages has quite recently been disproved by Dedekind (1908).

The development of the lens has been followed by C. Rabl (1898, 1899, 1900) throughout the entire vertebrate series. Of mammals he studied especially the rabbit, although the pig was also used for later stages ; human embryos were also investigated, and additional details as to these are furnished by the Normentafel of Keibel and Elze (1908). The earlier stages of development of the human lens are very similar to those in the rabbit. In an embryo of 4 mm. (Normentafel, Plate 10), the anlage of the lens is already recognizable as a thickened epithelial plate (Fig. 162) ; in an embryo of 4.9 mm. greatest length (Normentafel, Plate 14) there is a distinct lens plate (Fig. 163), and this is seen to be slightly concave in Fig. 164 (from the embryo of Normentafel 13). Figs. 166 a and b (from Normentafel 20) show a rather deep lens pit, the concavity being greater ventrally than dorsally. At the bottom of the pit are some cells, which have probably separated from the remaining cells of the lens plate in a manner similar to what was observed by Rabl in the rabbit. Fig. 167 a-c show the commencement of the closure of the lens vesicle, which, in the region where it has closed (Fig. 167c), has a triangular form. Figs. 168 a and b show a lens vesicle that has just closed. The closure does not take place at the centre, but more dorsally, and at the point of closure a knob of cells projects into the lumen of the vesicle, which also contains a number of degenerating cells.

Keibel Mall 2 174.jpg

Fig. 174. Lens of a human embryo of from 30 days.

Keibel Mall 2 175.jpg

Fig. 175. Section through the lens of a human to 31 days. X 130. (After C. Rabl, from Froriep embryo of 12.5 mm greatest length. (Hochstetin Hertwig's Handbuch, p. 225, Fig. 213.)

ter's embryo Mai, Normentafel of Keibel and Elze, Plate 56.) From a drawing kindly furnished by Professor Hochstetter. X 130.

Fig. 169 also shows degenerating cells in the lumen of the vesicle, which has now separated from the ectoderm; the proximal wall of the vesicle has become thickened and its cells are preparing to elongate into the lens fibres. A somewhat more developed stage is shown in Fig. 173, and even in this degenerating cells occur in the lumen. The lens shown under higher magnification in Fig. 174, taken from Rabl, is not quite so far advanced; in this there is seen in the lumen, in addition to some scattered cells, a mass of them lying on the distal wall. Rabl suggests that these cells may be an inheritance from remote ancestors and may have served in anamniote ancestors to separate the lumen of the lens provisionally from the outer world, just as occurs to-day in the Selachians. In a later stage of development the cells disappear; they are no longer to be seen in the stage shown in Fig. 175, which is taken from a human embryo of 12.5 mm. greatest length. The section is from the embryo from which the model shown in Fig. 172 was prepared (Hochstetter's embryo Ma., Xormentafel of Keibel and Elze, Plate 56). In many mammals such cell proliferations are much more abundant than in man and may fill the entire cavity of the lens pit.

Keibel Mall 2 176.jpg

Fig. 176. A lens at the time of the formation of the lens sutures (end of the third month). The right upper quadrant has been removed. One sees the lens epithelium, its continuity with the lena fibres at the equator.

The observations of C. Eabl (1898, 1899, 1900) and Herr (1893) have shown that in human embryos, as in those of other animals, the lens fibres after they have reached a certain length (in man about 0.18 mm.) no longer increase by division, but only grow in length. The cell multiplication which leads to the formation of additional lens fibres, and with it the occurrence of karyokinetic figures, now becomes limited to the anlage of the lens epithelium, and is found most active where this epithelium becomes continuous with the lens fibre mass. In this region there occurs as development proceeds a regular meridional arrangement of the epithelial cells, by which rows of fibres are produced, which may be termed the radial lamellae of the lens (Eabl, 1898, 1899, 1900). Even in embryos of 15 and 17 mm. greatest length Tandler finds the lens vesicle a solid structure (Normentafel of Keibel and Elze, Plates 60 and 65). The nuclei of the lens fibres have already at an earlier period arranged themselves in a curve convex toward the exterior (Figs. 174 and 175), and later these nuclei degenerate, beginning at the centre. Soon after the separation of the lens from the ectoderm a lens capsule cm. be recognized; in all probability this is formed in mammals and in man, as it has been shown to be formed in reptiles and birds, from cells of the lens anlage and not from mesoderm, which, however, comes into intimate relation with it as the tunica vasculosa lentis. At the end of the third month the formation of the lens sutures begins; they owe their existence to the peripheral fibres becoming longer than the central ones. The proximal suture, which is placed horizontally, is the first to appear, and then the distal one. This is represented in Fig. 176. Fig. 177 shows the transition of the lens epithelium into the lens fibres in a fetus at the beginning of the fourth month, after a preparation by Hochstetter ; it will serve as a complement to Fig. 176, which is schematic. The lens sutures become transformed in man into the lens stars, and first of all into triradiate stars, such as are seen in the human lens from the fifth month of development. Eabl (1900) has followed accurately in pig embryos the conversion of the linear sutures into the triradiate stars.

Keibel Mall 2 177.jpg

Fig. 177. Transition of the lens epithelium into the lens fibres, in a fetus at the beginning of the fourth month. From a drawing kindly furnished by Professor Hochstetter. X 200.

The lens is almost spherical in the third month, its proximodistal axis indeed slightly exceeding the equatorial diameter (Froriep, 1905 2 ). In an embryo of 19 mm. vertex-breech length Dedekind (1909) found the proportion of the sagittal to the equatorial diameter to be 1 : 1.14. Other data concerning the growth and modification in form of the lens will be given when the growth of the eye as a whole is under consideration. 15 We may now consider the development of the vitreous body, one of the most difficult problems of embryology. The account of it given here is based on the results obtained by the numerous workers who have attacked the problem within recent years and on my own observation, but at the same time I would point out that I do not consider the question as definitely settled. For this reason I shall add an account of some discordant views.

Both ectoderm and mesoderm appear to take part in the formation of the vitreous body, the retinal layer of the optic cup and the vasifactive mesoderm which enters the cavity of the optic cup with the vessels through the chorioidal fissure and around the edge of the lens; perhaps other mesodermal tissue also enters. The portion of the tissue that is derived from the retinal layer of the optic cup may be termed the primitive vitreous body. It appears upon the inner surface of the lens as soon as the cavity for the vitreous body begins to form between the lens and the retinal layer. At first non-cellular vitreous tissue arises from the whole extent of the retinal layer, but after the formation of the pars caeca, and with the progressive differentiation of the retina proper, the formation of this tissue ceases in the region of the latter ; only in the region of the pars caeca does it continue to form for some time, and from this region the fibres of the zona ciliaris arise. In what relation the mesodermic vitreous tissue, which begins to develop a little later than the ectodermic, stands to its predecessor and, accordingly, how the definitive vitreous body is f formed, remains doubtful to me. Froriep (1905 2 , p. 2-44) says on this point, "Both tissues appear to become most intimately united, in such a way that a new tissue element, the definitive vitreous bodv, is formed, the character of which is determined not by the v 7 7 w exceedingly delicate and perishable ectodermal portion, but by the strongly-developed mesodermal constituent." This would be a condition of great fundamental importance, a fact that was correctly perceived by Szily (1904, 1908), who regards the formation of the vitreous body merely as a special case of development of an embryonic supporting tissue. According to him, throughout the entire body of the embryo a non-cellular, fibrous supporting tissue is formed by the basal cells of all epithelial layers — no matter from which of the germinal layers they may have been formed — giving off fibrous processes which have arisen from intercellular bridges or protoplasmic processes. Later mesenchyme cells become associated with this non-cellular supportive tissue and an intimate protoplasmic connection develops between them and the fibres. In this way is formed the embryonic connective tissue with its two components, the mesenchyme cells and the fibrillar matrix. From now on the newly added cells take upon themselves the nutrition and growth of the fibres arising from the original sources. The primitive vitreous body, according to von Szily, is therefore formed not from the retina alone but from at least both the retina and the lens. In exactly the same manner is formed, for example, the tissue of the cornea. In this case also primitive fibrous connections are formed between the distal wall of the lens and the ectoderm lying over it; just as similar connections are made between the proximal wall of the lens and the retinal layer of the optic cup, and the stroma tissue of the cornea is formed by an association of mesenchyme cells with this primary fibrous substance. In his account of the development of the vitreous body and cornea Bryce (1908) has followed Szily, as has also V. Knape (1909), at least so far as the chick embryo is concerned. It seems to me, however, that such an idea is confronted with great difficulties, as, for instance, the relation between the cornea and the sclera.

  • 13 It may at least be mentioned here that in Amphibia the lens can be regenerated from the epithelium of the iris. An historical review of the observations on this point is given by Fischel (1909) in his work on the regeneration of the lens.

Dryault (1904) gives a very different account of the genesis of the vitreous body. Starting from the observations of Retzius (1894), he assumes the vitreous body to be primitively mesodermal, 18 but this becomes replaced by a secondary ectodermal structure derived from the retinal layer of the optic cup. In this way Cloquet's canal is formed, it being in reality not a canal at all, but the primary mesodermal vitreous body with its vessels, forced to the axis of the eye. " In fact, this cord represents the primitive vitreous body forced to the centre of the eye by the development of the definitive vitreous body." The wall of Cloquet's canal is the thickened layer of the secondary vitreous body that bounds the primary body. This is the condition of affairs at the sixth month of fetal life; after birth one finds no trace of the canal in man, the primary mesodermal vitreous body having been completely replaced by the secondary one.

Lenhossek (1903) regards the entire vitreous body as a derivative of the lens; but, on the other hand, the zonula fibres, according to him, are formed quite independently of the vitreous body and may grow out from the pars ciliaris of the retina. The hyaloid membrane has nothing to do with the vitreous body genetically; it is formed from the retina.

The older teaching, to which some recent authors, such as Carini (1899), Nussbaum (1900), and Spampani (1901), have returned, is to the effect that the 'vitreous body is a mesodermal structure which grows into the cavity of the optic cups through the chorioid fissure. That a mesodermal anlage of the vitreous body is not invaginated into the optic cup by the lens was long ago shown by Kessler (1S77) and myself (1886, 1895), and this has been confirmed by all recent careful investigations.

For further information on the question of the vitreous body mention may be made of the works of the following authors, in addition to those already cited: Tornatola (1897, 1898), C. Eabl (1898, 1899, 1900, 1903), Fischel (1900), Addario (1902, 1904-5), van Pee (1903), Kolliker (1903, 1904), Cirincione (1903W, 1904). Haemers (1903), Fuchs (1905), and Wolfrum (1907).

The vessels of the eye have an intimate connection with the 1S Dryault, however, did not study the early stages in which this condition is supposed to occur, and consequently begs the actual question.

formation of the vitreous body, since man, like the mammals in general, possesses in embryonic and fetal life an arteria lentis, ramifying in the capsnla vasculosa lentis and vasa hyaloidea propria. 17 Fig. 178 represents the vitreous body, lens, and retina of a human fetus of the sixth month, according to 0. Schultze. The a. lentis, before it reaches the lens, divides into the branches passing to the tunica vasculosa lentis ; the distal portion of the capsula vasculosa lentis (the so-called membrana pupillaris) has been removed together with the iris. The retina is reflected and is already vascularized up to the ora serrata, whereas in the third month of fetal life no retinal vessels are to be observed ; the existence of a membrana vasculosa retinae, which will be considered later, is denied by Versari (1903, 1909) for man. The vasa hyaloidea propria have already disappeared; their degeneration begins in the third month and proceeds from the periphery toward the centre. Fig. 179 shows the distal part of the tunica vasculosa lentis of a human fetus of the eighth month, in which marginal loops have already developed from the original uniform network. The blood supply of the tunica vasculosa lentis is threefold: it receives arterial blood from the proximal direction through the arteria lentis, from the equator through vessels from the arteriae hyaloideas propriae, and when these degenerate through the arteria lentis, and from in front through the long ciliary arteries (by means of the circulus iridis major). The venous return is entirely by way of the chorioid and falls directly into the venae vorticosae.

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Fig. 178. Vitreous body, lens, and the reflected retina of a human fetus of the sixth month. No vessels of the vitreous body are to be seen except the arteria lentis. C, corpus ciliare. (After O. Schultze 1892), Plate II, Fig. 9.) For further description see text.

"I follow the nomenclature of Froriep (1905 2 , p. 245), compare also H. Vircbow (1901), and use the term A. hyaloidea in a broad sense. It includes the following :

A. hyaloidea


f 1. Vessels of the ridge or shelf-like structures in 1 the suture of the optic cup.

(_ 2. Arteria lentis.

p . , i i 3. Vasa hyaloidea propria, x enpneral . •»-. . . •, * ( 4. Retinal vessels.

File:Keibel Mall 2 179.jpg

Fig. 179. Pupillary memorane of a human fetus of the eighth month, r, marginal loops. (After O. Schultze (1892), Plate I, Fig. 2.) Accordingly the growth zone of the lens, its equator, is supplied in a special manner ; in this region there is an exceedingly delicate network of exceptionally fine capillaries, which receives its blood from all three arterial supplies.

The earliest stages in the development of the eye-vessels are not yet sufficiently known, notwithstanding the work of Versari (1900 % 1900 % 1903, 1909) and Dedekind (1909). For the rabbit there exists a very thorough study by Fuchs (1905). According to him, the arteria hyaloidea arises as a blind bud from a circular vessel situated at the margin of the optic cup. This primary hyaloid artery enters the ventral portion of the cavity of the optic cup from the caudal side and forces a connection with the vessels of the choriocapillaris in the medial end of the chorioid fissure; the secondary hyaloid artery so formed unites later with the arteria ophthalmica interna. The arteria hyaloidea of the rabbit is, consequently, a complex vessel. The earliest development of the retinal vessels in man has been described by Versari (1903, 1904), but the description that follows here is based on the accounts given for mammals. Kessler (1877) has shown for the rat, and O. Schultze (1892) for the pig, the ox, and other mammals, that the retinal vessels arise independently of the arteria hyaloidea and ramify independently in the retina from the point of entrance of the optic nerve.

The observations of Voll (1892) agree with those of Schultze; he shows that mesoderm cells penetrate into the optic bulb with the arteria hyaloidea and form a swelling in the depressed centre of the papilla of the optic nerve, from which they spread out over the vitreous surface of the retina. Thus the membrana vasculosa retina? is fomied and this is soon vascularized from the papilla. In addition to the works mentioned, that of H. Virchow (1901) may also be consulted.

The development of the human retinal vessels differs, according to Versari (1903, 1904), from what has been described in mammals in several particulars. The cellular cushion of mesoderm that occupies the place of the later excavation on the papilla of the optic nerve does not extend out over the edges of the papilla upon the surface of the retina, but spreads out beneath the layer of nerve-fibres, so that from the beginning the vessels lie in the substance of the retina and there is no distinct membrana vasculosa retinae. The beginnings of the retinal vessels are not extensions of cilio-retinal arteries and retino-ciliary veins, but buds from the arteria hyaloidea and the two primitive veins of the optic nerve. In fetuses of 36 cm. the vessels have reached the inner reticular layer, and in those of 42 cm. the inner granular and even the outer reticular layer.

File:Keibel Mall 2 180.jpg

Fig. 180. The arteries of the base of the skull and of the eye in a human embryo of 22 mm. From an injected preparation, b., art. basilaris; c. a., art. cerebral, ant.; c. c. n. and c. c. t., art. ciliaris comm. nasal, and temp.; c. »., art. carotis intern.; c. i. r. a., art. carotis intern, ram. ant.; c. m., art. cerebral, media: c. p., art. cerebral, profunda; h., art. hyaloidea; <?., art. ophthalmica; r. p., ramus communicans posterior. (After Versari, 1900.)

Some figures taken from Versari (1900 *, 1903) will give a better idea of the relations that have been described and will serve as a complement to the text. Fig. 180 shows the injected vessels at the base of the skull in an embryo of 22 mm. vertexbreech length. From the a. carotis interna (c.i.) there arises on either side the a. ophthalmica, and each of these divides into a nasal and a temporal a. ciliaris communis (c. c. n. and c. c. t.) ; the nasal a. ciliaris communis gives off the a. hyaloidea (h.). In many cases the a. hyaloidea arises at the point of division of the a. ophthalmica. From the arteriae ciliares communes very fine branches are given off which supply the vascular network of the chorioid, but this is not well shown in the figure. At this time the majority of the vessels for the chorioid arise from arteriae ciliares communes during their course within the wall of the bulb, from the portion which later becomes the arteriae ciliares posteriores longae. Occasional branches are also given off before the arteriae ciliares communes enter the territory of the bulb ; thus even before a. hyaloidea there is given off from the a. ciliaris communis nasalis a small branch, which is to be regarded as an a. ciliaris posterior brevis. While fine branches pass to the chorioid from the arteriae ciliares posteriores longae in many mammals, even in the adults, they are no longer to be found in human fetuses of 5 cm. The vessels of the right eye of such a fetus are shown in Fig. 181. From the a. ophthalmica (o.) arise the two arteriae ciliares communes, a nasal (c. c. n.) and a temporal (c. c.i.), and from the nasal the arteria hyaloidea (h.) arises; the arteriae ciliares longae give off the arteriae ciliares posteriores breves {c.p.) and are then to be termed throughout their further course the arteriae ciliares posteriores longae (c.l.) ; o. is the peripheral continuation of the lentis, it enters the substance of the vitreous body it is surrounded by a swelling composed of cells, and in this later the retinal vessels will begin to develop. Even in a fetus of 10 cm. these vessels, as such, have not yet begun to form, as may be seen from Fig. 183 ; yet Versari was able to find, in the substance of the swelling which surrounds the a. hyaloidea in the region of the papilla of the optic nerve, some cell-cords, two of which were in connection with the wall of the a. hyaloidea. Attention should also be directed to the small venous vessels in the optic nerve and especially in the neighborhood of the a. hyaloidea (v. v.). From these the vena centralis retinae (v. c. r.) develops. In the substance of the vitreous body the companion veins of the a. hyaloidea, which here becomes the a. lentis, are completely wanting. Actual retinal vessels, permeable to blood, were first found by Versari in fetuses of 12 cm.; they are shown in Fig. 184 (a. r. and v. r.). The a. hyaloidea seems to be dilated in a spindle-like manner at the point of origin of the retinal arteries (a. r.), and from this point onward it may be termed the a. lentis. The development of the v. centralis retinas has made considerable progress; Fig. 185 shows the appearance it presents in sections. The figure is reconstructed from some sagittal sections through the eye of a fetus of 13 cm.

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Fig. 181. The vessels of the right eye of a 5 cm human etus. From an injected preparation, c. I., art. ciliar. post, long.; c. p., art. ciliar. post, breves; o., continuation of the art. ophthalmica. The remaining letters have the same significance as in Fig. 180. (After Versari, 1900 1 .)

Fig. 182 shows a sagittal section through the point of entrance of the optic nerve into the bnlb in a 7 cm. fetus. The arteria hyaloidea (h.) is cut longitudinally; where, as the art.

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Fig. 182. Sagittal section through the point of entrance of the optic nerve in a human fetus of 7 cm. H., vitreous body; h., art. hyaloidea; W., cellular swelling in which the retinal vessels are beginning to form. (After Versari, 1903.)

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Fig. 183. Injected preparation of the eye vessels of a 10 cm fetus, c. p., principal stem of the art. ciliares post.; h., art. hyaloidea; r., retina; v. c. r., vena centralis retinae; v. v., veins surrounding the art. hyaloidea from which the vena centralis retina? arises.

File:Keibel Mall 2 184.jpg

Fig. 184. Injected preparation of the eye vessels of a 12 cm fetus, a. r. and v. r., arteriae and venee retina?; the remaining letters as in Fig. 183. (After Versari, 1903.) the veins (v. r.) are represented as black and the arteries (h., a. I., a. r.) as gray. Fig. 186 a-c represent sections through the injected retina of fetuses of 19 cm., 36 cm., and 42 cm. One may perceive from these how the retinal vessels penetrate more and more deeply.

Greater or smaller remnants of the embryonic vessels occasionally persist in man; they are inhibition structures and may have a practical importance. Compare on this point Hippel (1900) and Bruckner (1907).

We come now to a consideration of the differentiations which the optic cup and its individual parts undergo during the further course of development. The outer (proximal) layer of the optic cup becomes transformed into the pigment epithelium of the retina. The pigment makes its appearance in embryos of from 7 to 9 mm. greatest length (compare Normentafel, Plates 29^43), and first of all in the region of the pupillary border, whence it extends backward towards the optic stalk. 18 The retinal layer becomes differentiated into the pars optica and the pars caeca, this latter again giving rise to the pars ciliaris and the pars iridica.

The pars optica is separated from the pars caeca by an ora serrata even in the fetus, and 0. Schon (1905 l > 2 ) in denying the existence of an ora in the new-born child is undoubtedly incorrect, as the observations of 0. Schultze (1902) and others have shown. 19 The separation is associated with the formation of the ciliary body and its ciliary processes. In the fourth month of development the margin of the retina lies at the ciliary margin of the iris, but the more the ciliary body with its processes enlarges, the more the margin of the retina retreats proximally, and, since the retinal layer does not keep pace with the ciliary body in the increase of its surface, there results a corresponding thinning of the layer. The degree of development of the ora serrata also varies greatly in the fetus. Fig. 187 shows the iris, the corpus ciliare, and the the tips of the teeth of the ora serrata into the orbiculus ciliari.-, are relics of the greater thickness which the retina originally possessed throughout the entire region of the orbiculus; the streaks vary greatly in their development in different individuals.

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Fig. 185. Section through the point of entrance of the a. hyaloidea into the optic bulb of a fetus of 13 cm, reconstructed from several sagittal sections, a. I , art. lentis; a. r., retinal artery; H., vitreous body; h., art. hyaloidea; W., swelling around the point of entrance of the a. hyaloidea, in which the retinal vessels have been formed. (After Versari, 1903.)

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Fig. 186 a-c. Sections through injected retime; to the right the layer of nerve-fibres, to the left the outer layer which gives rise to the rods and cones. One sees the gradual penetration of the vessels. Fig. 186a : Sagittal section of the retina in the neighborhood of the optic papilla, from a fetus of 19 cm. Fig. 186b: A similar section from the posterior hemisphere of the bulb of a fetus of 36 cm. Fig. 186c: A section similar to the preceding for a fetus of 42 cm. (After Versari, 1903.)

  • According to Ucke (1891), the pigment extends into the optic stalk in embryos of the chick and sheep, and 0. Lange (1908, p. 12) has reported the same thing for man.

File:Keibel Mall 2 187.jpg

Fig. 187. Iris and corpus ciliare of a fetus in the second half of the fourth month. (After O. Schultze (1902), Plate I, Fig. 5.)

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Fig. 188. Iris and corpus ciliare from a prematurely born fetus of the eighth month. (After O. Schultze (1902), Plate I, Fig. 6.) distal edge of the retina, its ora serrata, of a fetus in the second half of the fourth month. An unusually strong development of the teeth of the ora serrata is shown in Fig. 188, from an eight months' fetus prematurely born; almost all the teeth extend through the entire breadth of the orbiculus ciliaris. Streaks of pigment, in which the pigment layer of the retina is thickened to form ridge-like structures and which very usually extend from

  • Quite recently 0. Lange U90S. p. 20) seems to have returned to Sehon's view, but certainly without sufficient reason.

The pars optica of the retina differentiates in a proximodistal direction, the maculo-papillary region being the first to develop completely. Sections through the retina of an eight weeks' embryo still present, according to Chiewitz (1887), a purely epithelial character, except for the layer of nerve-fibres. Two principal layers of nuclei are separated by a clearer intermediate zone, in which more scattered nuclei (spongioblast nuclei) occur. At two and one-half months before birth all the layers of the retina are complete. An intermediate granular layer first appears in a five months ' fetus at the spot where the macula lutea will later form, and in the same region the first cones appear at a slightly earlier date (17 weeks 20 ). The fovea centralis begins to form after the sixth month and is present in fetuses of seven and a half or eight months. During its formation the outer fibre layer develops in the outer granular layer and the transitory radial fibre layer, which later disappears but is still present in the nine months' fetus, appears in the inner granular layer between the spongioblasts and its other elements, the layer being traversed obliquely by the elongated and diverging radial fibres. The layer of multipolar ganglion-cells at its first formation consists of about seven tiers of cells, but as the entire layer becomes increased in surface extent its elements separate to form a single layer, the original condition persisting only in the macula lutea.

The fovea centralis has, contrary to earlier opinions, nothing to do with the chorioidal fissure. Its formation begins in the seventh month and proceeds from the inner toward the outer layers (Chiewitz, 1887). Its appearance is preceded by a thickening of the corresponding region, so that the concavity is a secondary formation. Chiewitz suggests that individual variations in the behavior of the cerebral layer at the bottom of the fovea may be due to persistence of an earlier or later stage of embryonic development.

The histological differentiation of the retina has been more thoroughly followed by Ramon y Cajal (1896) in the cat, dog, rabbit, calf, and mouse. Fig. I89 represents a section through the retina of a new-born cat. in which the differentiation is taking place. The multipolar cells are the first to develop; these next form their axis-cylinder processes and then the dendrites, these latter at first extending out on all sides, though later only the ascending (distal) ones persist, the others atrophying. At an early date those bipolar cells that are destined to become rod cells can be distinguished from those that will form cone cells. Both first produce the proximal process (unipolar stage) which comes into connection with the membrana limitans externa, but the cone cells have a greater amount of protoplasm and consequently stain more darkly with Golgi's silver method. The distal processes arise later; they develop to various degrees and may occasionally extend almost to the zone of multipolar cells. The nuclei of the cone cells finally approach the membrana limitans externa and then their proximal (descending) processes all extend to the same level. Rod and cone cells are peculiar structures that can be classified neither as nerve- nor neurogliacells. Finally the rods and cones develop. The horizontal cells at first give off processes in all directions, but later their cell bodies become smaller and the dendrites spread out in a single plane, that of the outer reticular layer, their axis-cylinder processes at the same time increasing in length. The Mullerian cells correspond to the glia-cells of the rest of the central nervous system; they differentiate at an early stage and traverse the retina from the lamina limitans interna to the lamina limitans externa. Their nuclei are at first scattered through the entire thickness of the retina, with the exception of the layer of multipolar ganglion-cells, but later they assemble in the inner granular layer. At times two nuclei may be found in many of the cells, a condition which Ramon regards as an indication of cell multiplication.

  • According to Falchi (1888 12 ), the rods have begun to form in a fetus of 21.3 em.

Pigment is formed in the pars cceca of the retina, the pigment extending over the margin of the optic cup into it and reaching finally the region of the corpus ciliare. Up to the end of the seventh month Szily (1902 ** 2 ) finds between the two layers, where they pass into one another, a cavity, which he regards as a circular sinus. With the disappearance of this sinus the anterior epithelial layer sinks into the concavity of the margin of the optic cup. In a fetus of 10 cm. the outer layer of the cup is pigmented only up to the region of the peripheral border of the circular sinus. From here outward the pigment diminishes in amount and is continued over the edge of the cup into the inner lamella only as a few granules. At the middle of the fifth month it has reached to about the middle of the iris; during the latter portion of intra-uterine life it reaches the region of the ciliary processes, but does not actually extend into these even in the new-born child.

The most noteworthy point in the development of the eye, and one that is full of significance for histogenesis in general, is the fact that the musculus sphincter and the musculus dilator pupillae take their origin from the iris portion of the outer (proximal) layer of the optic cup. These muscles are therefore formed from ectodermal epithelial cells. This mode of development of the dilatator was first recognized by Grynfeltt (1898 1 - 2 ) in the rabbit, in which it begins to occur at 14 days after birth; later Nussbaum (1900) noted its occurrence in birds and mammals (mouse). Similar results have also been obtained in man. According to Heerf ordt ( 1901 1 ) , the formation of the muscle-cells begins in the 24-30 week of fetal life. The nuclei withdraw from the outer ends of the cells, and the non-nucleated, strongly pigmented portions of the cells fuse to form a diffusely pigmented lamella, whose protoplasm retains its continuity with the nucleated portions of the cells. Then the non-nucleated portions arrange themselves radially, and fibres, also directed radially, appear in them and later arrange themselves in bundles. The pigment collects in the nucleated portions of the cells, and each of the fibres then stands in connection with a pigmented, nucleated portion of a cell, which lies on the proximal side of the fibre and with it forms a typical, epithelial, smooth muscle-cell. The development of the musculus sphincter pupillae has been followed in man by Szily (1902 h 2 ) and Herzog (1902). Szily finds its earliest anlage in a fetus of 10 cm. in a very slight aggregation of irregularly placed epithelial nuclei at the margin of the optic cup (Fig. 190). The corresponding cells grow towards the ciliary body as a lamella-like process, and an elongation of them becomes noticeable very early. The pigment, which even at first was but sparingly developed, later vanishes almost completely. In fetuses of eight and nine months the relations with the dilatator have developed, and even in the new-born child the muscular sphincter is still in intimate connection with the epithelium at the pupillary margin. Figs. 191, 192, and 193 show some stages in the development, after Szily. The optic nerve develops from the stalk of the optic cup, this, however, giving rise only to the neuroglial scaffolding, the nerve fibres arising for the most part from the multipolar cells of the ganglion retinae and therefore growing centripetally ; in addition there is a much smaller number of centrifugal fibres, which have their terminations in the retina. I first (1889) called attention to the fact that in reptilian embryos the first optic-nerve fibres grew from the retina centrally; then His (1890) arrived at the same result for man and Froriep (1891) confirmed it for Selachians. As the result of numerous observations, this condition seems to me to be general. The existence of nerve-fibres in the distal portion of the optic nerve is noted as occurring in an embryo of 15.5 mm. vertex-breech length in the Normentafel of Keibel and Elze (Plate 61) ; in an embryo of 17 mm. greatest length they have reached the recessus opticus, although in another of 20 mm. greatest length they are still remote from that point (Plate 65). For a detailed account the Normentafel may be consulted, and itis also shown there how the lumen of the optic stalk gradually becomes obliterated. Figs. 194 and 195 show sections through the optic nerve of a mouse embryo of 12 days, the section represented in Fig. 194 being proximal to that shown in Fig. 195. A connects

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Fig. 189. Section through the retina of a new-born cat. a and 02, epithelial cells with two nucleiepithelial cell with peripheral nucleus; c, epithelial cell of the ordinary type, the nucleus lying at about the middle of the retina; d, embryonic cone cell in the unipolar stage; e, rod cell in the corresponding stage; /, rod cell with a deeply seated cell body; g, cone cell in the transition stage; h, amacrine cell; i, ganglion cells; J, displaced amacrine cells; k, embryonic cone cell whose cell body lies near the outer reticular layer* 2 , a similar rod cell. (After Ramon y Cajal (1896), Plate XII, Fig. 1.)

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Fig. 190. Margin of the optic cup of a fetus of 10 cm. I. E., inner epithelial layer; A. E., outer epithelial layer of the optic cup; R. s., circular sinus; Sph. A., anlage of the sphincter; P. m., pupillary membrane; C. c, corpus ciliare; C, cornea. (After Szily, 19021.)

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Fig. 191. Radial section through the aniage of the iris of a 10.2 cm. fetus. /. E., inner, -4. E.. outer epithelial layer of the optic cup; R. s., circular sinus; Sph., sphincter; Istr., stroma of the ir s; P.m., pupillary membrane (After Szily, 1902.)

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Fig. 192. — Radial section through the anlaee of the iris of a fetus of 24 cm. I E., inner epithelial layer; A.E., outer epithelial layer; R s, circular sinus; Sph. Sphincter; Istr., stroma of the iris; P.m., pupillary membrane. (After Szily, 1902 1 .)

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Fig. 193. — Radial section through the sphincter region of the anlage of the iris of a new-born fetus. /. E., inner epithelial layer; A. E., outer epithelial layer; Sph., sphincter; Dil., dilator; Psp., pigment spur; Istr., stroma of the iris.

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Fig. 194. Section through the optic nerve of a mouse embryo of 12 days. (After Kruckmann, 1906.) tive-tissue scaffolding is later added to the neuroglial one ( Jacobi, 1905, Kruckmann, 1906).

The chorioid, together with the corpus ciliare, the musculus ciliaris, the iris, and the sclera, develop from the dense mesodermal tissue that surrounds the optic cup. Somewhat less simple is the development of the cornea. Its mesodermal foundation must first penetrate between the distal surface of the lens and the ectoderm, and in this tissue the anterior chamber of the eye, which separates the corneal anlage from the distal layer of the capsula vasculosa lentis, is formed. Mention has already been made (p. 233) of the special view as to the development of the cornea and connective tissue in general advocated by Szily (1904, 1908). The vessels of the chorioid and of the choriocapillaris develop without any complications from the abundant vascular supply which, even at an early stage, surrounds the optic cup.

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Fig. 195. Section through the optic nerve of a mouse embryo of 12 days; the section is distai to that shown in Fig. 194. The lettering in both figures has the following meaning: a., epithelial cells, the so-called primitive glia; b., the beginning of the vacuolization and extension phenomena in the protoplasm of the glia cells as a result of the penetration of neurofibrillar; h., cells of the primary glia in which the neurofibrils (n.) first appear near the limitans superficialis (L. s.); L. s., limitans superficial of the optic nerve; n., neurofibrillar; O., lumen of the optic stalk. (After Kriickmann, Plate IX, Fig. 8.)

The musculus ciliaris undoubtedly develops from the mesenchyme tissue which is arranged in a lamellate manner around the optic cup (Herzog, 1902). In the region of the sclera this mesenchyme secretes collagen substance and separates into the fibrillar sclera tissue and the stroma of the chorioid which is destitute of collagen, with the exception of what is contained in the walls of the blood-vessels. The conversion of the lamellated mesenchyme tissue into smooth muscle tissue is associated with the preservation of the form of the cell body as well as of the nucleus and with the persistence of the protoplasmatic characters of the cell body, whereby the nucleus and cell body undergo a variable increase in size. At the same time the cells assume a closer arrangement and become more densely aggregated in the line of the pull of the later muscle. The first formation of the ciliary muscle is found in fetuses of 12 cm. and its development is completed in the seventh or eighth month.

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Fig. 196. Section through the anterior part of the bulbus oculi of an embryo of 23 mm vertex-breech length (embryo Ti, from the collection of the first anatomical Institute in Vienna; Normentafel of Keibel and Elze, Plate 79). v. K., anterior chamber. X 80. (From a drawing kindly furnished by Professor Tandler).

In the sixth month the lamellate mesenchyme tissue of the uvea becomes looser by the development in it of numerous bloodvessels ; as a result the layered mesenchyme tissue within the layer occupied by the large vessels assumes what Herzog (1902) has termed a "reticular formation," its cells becoming stellate pigment-cells. External and internal to the vessels, those of the choriocapillaris excepted, the tissue retains its lamellate arrangement and differentiates into cells which Herzog regards as endothelial, into flat cells which form sheets, and into a peculiar kind of cells of doubtful character but which Herzog regards as rudimentary muscle-cells.

The description which follows, of the development of the anterior chamber and of the structures in the angle of the chamber, is based essentially on the observations of Seefelder and Wolfram (1906), but the work of Gabrielides (1895 1 > 2 ), Jeannulatos (1896 1 ' 2 ), and Fritz (1906) may also be mentioned. In the Normentafel of Keibel and Elze, on Plate 79, the existence of an anterior and posterior chamber is shown in an embryo of 23 mm. vertex-breech length (Tandler), and Plate 84 shows them in an embryo of 26 mm. greatest length. Fig. 196 represents a section through the anterior part of the bulbus oculi of the embryo figured in Plate 79 of the Normentafel. I am indebted to the kindness of Professor Tandler for the drawing. The anterior chamber (v.K.) is plainly recognizable in the figure ; when, therefore, Seefelder and "Wolf rum recognize Descemet's endothelium in a fetus of 53 mm. and Descemet's membrane in one of 70 mm., but fail to perceive any indication of the chamber, it must be supposed that the latter must again become for a time indistinct and that these authors have not really observed its first formation. At the end of the fourth month Descemet's membrane is formed throughout its entire width and the sinus of Schlemm is indicated. At the end of the fifth month the ciliary processes 21 are recognizable and also the sclerocorneal network that fills the outer portion of the chamber 21 Szily (1902 *, p. 168) notes that the formation of the ciliary processes is not limited exclusively to the region of the ciliary body in the embryo, but also takes place in the region of the primitive anlage of the iris, relying for proof of this in a section through the iris of a 19 cm. fetus, which he reproduces in his fig. 3. where it abuts in the sclera, but the ligamentum pectinatum iridis, situated more internally, is not yet visible. According to Seefelder and Wolfram, the first indication of the anterior chamber is to be seen at this time as a circular cleft in the region of the pupillary border of the iris. At the beginning of the sixth month the ligamentum pectinatum is also formed. In the middle of the same month the portion of the anterior chamber in front of the distal pole of the lens can be detected, but it is as yet narrow. At the beginning of the seventh month the scleral swelling becomes evident and the sinus of Schlemm becomes wider. In the eighth month the chamber becomes noticeably deeper and at places the formation of the ligamentum pectinatum pushes its way, wedge-like, between the longitudinal and circular bundles of the ciliary muscle. In the ninth month the membrana pupillaris, together with the capsula vasculosa lentis, has disappeared and the ligamentum pectinatum has become smaller. In the new-born child remains of the ligamentum pectinatum are still present and the angle of the chamber is, as a rule, acute. As regards the cornea I would note that in embryonic and fetal life it is not vascularized, as was formerly sometimes supposed (Hirsch, 1906).

The eyelids make their appearance in embryos of about 20 mm. greatest length (compare Normentafel, Plates 67, 68, 70, and 71). In the description of their development I follow Ask (1907, 1908) for the most part, but would make mention also of the observations of Contino (1908).

The lid margins are already completely fused in a fetus of 33 mm., the epithelial fusion extending from the sides towards the middle of the palpebral fissure. In later stages it involves not only the actual margins of the lids but also the neighboring portions of the epidermis and extends both nasally and temporally far beyond the corresponding palpebral angles (Schweigger-Seidel, 1866). The separation of the lids is accompanied by a process of cornification (compare also Seiler [1890] for the dog and Nussbauni [1900] for 'the mouse), which first affects the intermediate cells most distant from the basement membrane. It extends not only from the outside (front), but also from the cornified wall cells of the hair canals of the eyelashes, from those of the hairs developing within the zone of fusion and from the corresponding cavities at the mouths of the sebaceous glands of the lids; finally it also begins independently at the innermost part of the zone of fusion, where the formation of a deep groove lined with epithelium of the epidermis type precedes the complete separation of the lids.

The development of the cilia resembles that of the other body hairs; the ciliary sudoriparous glands (Moll's glands) arise as outpouchings of the basal cells on the anterior sides of the anlage of the cilia, immediately in front of the anlagen of the ciliary sebaceous glands. The tarsal glands arise from the epithelium of the innermost (most posterior) portions of the fused margins of the lids, as epithelial buds (Konigstein, 1884). The glands of the upper lid exceed those of the lower in length only after the middle of embryonic life. The first anlage of the tarsus appears some what early as an aggregation of mesoderm cells in the posterior portions of the lids, but it obtains its definitive character only after the further development of the tarsal glands.

The caruncula lacrimalis takes its origin from the lower lid, whose most nasally situated tarsal glands and ciliary anlagen are separated from those of the rest of the lid by the opening of the lower lachrymal canal, which at first is situated relatively some distance laterally. This portion of the lid becomes pushed nasally and deeply to form the carunculi, and the connecting folds of the lower fornix are the result of the covering in of the caruncle. Only exceptionally do anlagen of ciliary sudoriparous glands develop in the caruncula. The nictitating membrane appears soon after the lids and is quite independent of the caruncula, which forms only much later. It is relatively larger during certain stages of fetal life than it is later, and it seems regularly to develop a rudimentary gland. Fig. 197 shows the relation of the openings of the lachrymal canals on the upper and lower lid of a fetus of 40 mm.; the position of the future tarsal glands, which are lacking at this stage, is represented diagrammatically. Fig. 198 shows the openings of the lachrymal canals and the grouping of the tarsal glands in a fetus of 19 cm. ; the anlage of the caruncle is separating from the lower lid. Fig. 199 shows a model of the eyelids of the right eye in a fetus of 25 cm., seen from the inside; the anlage of the caruncula is distinctly separated from the lower lid.

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Figs. 197 and 198. Explanation in the text. In both these figures the lids which are actually fused are shown separated. (After Ask, 1907.)

Keibel and Elze found the earliest anlagen of the lachrymal glands in embryos of from 22 to 26 mm. (Normentafel, Plates 80, 82, 83, 84), as knob-like ingrowths from the conjunctival epithelium. Their further development has recently been thoroughly studied by Speciale-Cirincione (1908 1 ' 2 ) 22 . He finds the gland at a somewhat later stage than Keibel and Elze, in a fetus of 32 mm., about the 70th day of development. Five or six ectodermal ingrowths of it becomes completed in fetuses of 60 mm. The orbital part is formed exclusively by the portions of the first five or six primordial cords which lie on the far side of the interglandular septum; the palpebral portion, by branches given off before the cords perforate the interglandular septum and by the buds and branches of the later-formed primordial cords. Fig. 201 shows these relations. In the cords, which are at first solid and are formed of large, polyhedric cells with round nuclei and homogeneous protoplasm, a lumen is formed in fetuses of 50 mm. by the breaking down of the central elements, and after the appearance of the lumen one can plainly distinguish, according to Speciale-Cirincione, two layers, the layer of the secreting cells and that of the basal cells.

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Fig. 199. Explanation in the text. (After Ask, 1906.) the conjunctival epithelium form very quickly one after the other in less than a day. Their position is shown in Fig. 200. They are situated in the upper part of the outer conjunctival fornix at the point where the conjunctiva of the lid passes over into the fornix. The anlagen are at first knob-like, but become quickly (in the course of a few hours) transformed into club-shaped structures ; these grow exclusively in length and in a few days are converted into epithelial cords destitute of a lumen. The first branchings of the five or six first formed primordial cords are observed in fetuses of 30 mm. ; in those of from 40 mm. to 60 mm. additional anlagen appear, which begin to branch in fetuses of 54 mm. In fetuses of 38 mm. the division of the lachrymal gland into an orbital and a palpebral portion by a laterally directed expansion of the tendon of the levator and by Tenon's capsule has begun, and J While these pages were being printed there appeared the careful paper of Ask (1910), in which, in addition to the development of the lachrymal gland proper, that of the conjunctival accessory glands (glands of Krause and Wolfring) is also described. The comparative anatomical relations are also considered.

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Fig. 200. Reconstruction of the conjunctival sac and the lachrymal gland of a fetus of 32 mm. (sitting height probably) seen from the outer surface. Aes., external anele: Corn., cornea; Ecpi., ectoderm of the conjunctiva of the lower lid; Ecps., ectoderm of the conjunctiva of the upper lid; Fs., external fornix; Fi., internal fornix; Gpi-e, epidermis (ectoderm) buds arising from the upper external angles of the fornix and representing an early stage in the development of the lachrymal gland; Gpi is club-shaped, Gp2— i are small knobs, Gp5-6, are slight outgrowths; Mpi., margin of lower lid; Mps., margin of upper lid; Sc, sclera. X25 (After Speciale-Cirincione, 1908 2 .)

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Fig. 201. Reconstruction of the lachrymal gland of a fetus of 50 mm (probably sitting height). Six anlagen (primordial cords) traverse the interglandular membrane (Mig.) and, together with their branches, form the orbital portion of the lachrymal gland. Other anlagen do not reach the interglandular membrane (Mig.) ; they form the palpebral portion of the gland, together with branches given off from the cords intended for the orbital portion, before they perforate the interglandular membrane. Gpi, a primordial cord with branches only at its orbital end; Gv2-s, cylindrical primordial cords richly branched at their orbital ends and giving off buds from their portions which traverse the lid; Gpt, primordial cord which divides into two secondary cords in the palpebral portion of the gland, the branches of these lying in the orbital portion; Gs., secondary cords; Gt., tertiary cords; Ecp., epithelium of the palpebral conjunctiva; Mig., interglandular membrane ("lateral expansions of the levator") ; Pep., branched primordial cords belonging to the palpebral portion of the gland; PGp., primordial buds belonging to the palpebral portion of the gland; fit., terminal branches; Sc, sclera. X25. (After Speciale-Cirincione, 1908 2 .) The accessory conjunctival lachrymal glands are formed, according to Falchi (1905), in a fetus of 31 cm. In the new-born child the lachrymal gland has not yet reached the height of its development, having only one-quarter to one-third the size of the adult gland (Kirschstein, 1894) and differing also in the appearance of its cells (Axenfeld, 1899 23 ) ; that it actually is without function at this time has been correctly denied (De "Wecker, 1899, Baratz, 1902). G-oez (1908) has quite recently reinvestigated the lachrymal gland at different ages and in general confirms the results of Kirschstein (1894). From the first year onward there is a gradual change in the histological structure of the gland. "The height of the glandular epithelium becomes gradually less and the lumen becomes correspondingly wider, and at a more advanced age the gland assumes quite an altered appearance, owing to a strong increase of the interstitial connective tissue. With advancing age a distinct involution of the gland occurs." The mode of formation of the lachrymal passages, the ductus nasolacrimalis, the saccus lacrimalis, and the lachrymal canals are also quite clearly understood in man (Fleischer, 1906, and Matys, 1906). As Born (1879, 1883) and his pupil Legal (1881, 1883) showed for the Sauropsida and Mammals, so too in man the ductus nasolacrimalis arises as a solid epithelial bud, which grows down freely through the mesoderm to the nasal cavity from the conjunctival portion of the lacrimo-nasal groove. Consequently the lachrymal canals do not represent the original connection of the anlage with the conjunctival epithelium, but this original connection is lost; the canals bud out from the still solid ductus lacrimalis and secondarily acquire their connection with the margins of the lids.

  • Compare also Schirmer in Grafe-Samisch. Handbreb der sresamten Augenheilkunde. 2d edition

Accounts of the conditions in mammals, in which the processes are essentially the same as in man, have been furnished by Fleischer (1906) for the pig and rabbit and by Matys (1905) for the marmot (Spermophilus citillus) and the pig. In the apes, according to my own observations (1906 1 ), the processes take place as in man. Thus, in a Macacus cynoinolgus of 13.5 mm. greatest length (Plate 14) the solid ductus nasolacrimalis, whose distal end is still far from the nasal cavity, has lost its connection with the ectoderm at its orbital end and divides there to form the anlagen of the two lachrymal canals (compare also Plates 17, 18, 20, 21, 22). In an embryo of Nasalis larvatus of 25.2 mm. greatest length (Plate 23) the ductus nasolacrimales do not quite reach the epithelium of the nasal cavities, the lachrymal canals have reached the epithelium but have not yet fused with it. Slightly less developed is a Semnopithecus maurus of 26 mm. greatest length (Plate 24).

Early anlagen of the ductus nasolacrimales in embryos between 9 mm. and 11 mm. greatest length are shown in the Normentafel of Keibel and Elze in Plates 47, 48, and 49. In the embryo shown in Plate 84 (26 mm. greatest length) neither have the ductus nasolacrimales quite reached the epithelium of the nasal cavities nor the lachrymal canals that of the margins of the lids. According to Cosmettatos (1898), the lachrymal passages acquire a lumen in the third month of fetal life. It appears first in the upper portion and then proceeds from above downward, and is completed shortly before birth. According to Monesi (1904), the opening at the lower end of the duct is formed by the medial wall becoming broken through, and the groove which frequently occurs below the opening is thus explained as the lateral wall of the portion so opened.

No satisfactory account as yet exists as to the development in man of the muscles that move the bulbus oculi.

This is true with regard to the mammals, in general, notwithstanding the work of Corning (1899) on the rabbit and of Reuter (1897) on the pig." The question of the development of the eye-muscles is associated with the difficult problem of the metamerism of the head. In general, following van Wijhe (1882 '), the oculomotor musculature — i.e., the museulus rectus superior, inferior, and interims and the museulus obliquus inferior — is supposed to be derived from the first head metamere, the museulus obliquus superior, supplied by the trochlearis, from the second, and the museulus rectus externus, supplied by the abducens, from the third. In reptilia and birds the oculomotor musculature arises from the wall of the head cavity, which, however, does not always reach a complete development. In Lacerta the head cavities are formed in embryos with one or two primitive somites from the entoderm at the anterior end of the chorda. This anlage forms a cell mass extending laterally on either side and possessing only a cleft-like cavity or indeed none whatever; for a considerable time it remains connected with the tissue from which it is formed by a cord of cells (the intermediate cell cord). Similar conditions have also been observed in mammals (the rabbit) by Corning (1S99) and in birds (the duck) by Rex (1897). Later a hunen, which soon becomes much enlarged, appears in each of the lateral masses, and while the intermediate cord degenerates, the epithelial walls of the head cavity give rise to the oculomotor musculature. At its dorsal and ventral portions a slight outpouching appears, from which a proliferation of epithelial cells takes place, and there is thus formed a dorsal and a ventral muscle anlage. These separate completely from the epithelium of the walls of the head cavities and grow toward their final points of origin and insertion, that is to say, toward the anterior end of the chorda and toward the bulbus. The walls of the head cavity take no essential part in the formation of the mesenchyme, but those portions that are not used in the formation of the muscles persist in the midst of the ingrowing mesenchyme and are to be recognized at a relatively late period as cords or bars of epithelial cells. The branches of the oculomotor nerve lie at first on the surfaces of the muscle anlagen that are turned toward the bulbus. The museulus rectus externus arises in Lacerta from a mass of cells, whose epithelial arrangement indicates their derivation from a head cavity. The anlage lies at first on the lateral and posterior wall of the oculomotor cavity, and the museulus obliquus superior arises from the dorsal portion of the anlage which grows out above the bulbus. It separates from the parent tissue and secondarily grows to its later points of origin and insertion.

Reuter's investigations began, unfortunately, with a somewhat advanced stage, with a pig embryo of 22 days. Such an embryo already shows the anlage of the eye musculature with the corresponding nerves, while nothing is yet to be seen of the mandibular musculature. The anlage has the form of a somewhat thick, stalked demilune, the abducens nerve passing to the stalk from behind : the oculomotor passes to the anlage from above, and the trochlearis somewhat later becomes connected with the uppermost point of the demilune. The two limbs of the demilune surround the optic stalk. In the further course of development the anlage of the musculature wanders forward toward the optic nerve and loses its posterior limb (stalk), which is pushed forward by the anlage of the neighboring vena jugularis. The two remaining limbs unite to form a ring, which gradually assumes a cup-like form and surrounds the anlage of the eye. Sheet-like anlagen, corresponding to the later muscles, now grow toward the bulbus, the recti and obliqui forming first. The separation of the individual muscles proceeds from the bulbus toward the apex of the orbit, the connective tissue which occurs between the various forward extensions penetrating the muscle mass and bringing about its division. Before this is completed, however, the museulus retractor bulbi separates from the anlage of the musculi recti and. as the last of the eye muscles. the levator palpebral superioris arises from the medial border of the rectus superior. Corning (1899. p. 65) has criticised Reuters results, on the ground that he dor

all the muscles from a common anlage. I cannot here discuss the very complicated problems connected with these muscles which yet await solution, but would mention for reference, in addition to the works already cited, those of van Wijhe (1882 2 ), Miss Piatt (1891, 1897), C. K. Hoffmann (1896, 1897), Neal (1897, 1898), Sewertzoff (1895, 1S98), Oppel (1890), and Corning (1900). Attention may also be called to the work of Nussbaum (1896, 1899, 1900), who, on the basis of the law of nerve and muscle growth discovered by himself, concludes that the musculus obliquus superior of the mammals is not quite equivalent to that of the lower vertebrates, but contains an additional element. If the portion of a nerve between its central origin and the point of entrance into the muscle be termed its extramuscular portion, and its ramifications within the muscle its intramuscular portion, then the intramuscular portion will show the direction of growth of the striated muscle-fibres. We can in this manner recognize the portion of the muscle that has been formed after the union of the nerve with the muscle. The points of entrance of the nerves into the four recti muscles lie in the mammals and in man near the optic foramen on the inner surfaces of the muscles; in the case of the obliquus superior the nerve enters the outer surface near the optic foramen, and the nerve reaches the obliquus inferior only about the middle of the muscle belly. It may therefore be supposed that the recti and the superior oblique muscle gradually approach the corneal margin during embryonic growth. Nnssbaum has been able to show this in various mammals. The obliquus superior, like the musculi recti, grows from the back part of the orbit toward the bulb, and its terminal tendon gradually passes from the anterior into the posterior portion of the bulbus oculi.

Zimmermann (1898) has described in man structures which are perhaps to be regarded as the remains of a head cavity. In an embryo of 3.5 mm. nape length there were several (on the right three, on the left seven) clearly denned, small, completely closed vesicles, whose walls were formed of epithelium-like cells, situated near the epithelium of the mouth cavity, lateral to the internal carotid artery and Bathke's pouch, and somewhat behind the eye vesicle, in a region where the mesoderm was slightly richer in cells than elsewhere. Henckel's observations (1898) show that the musculus levator palpebrse superioris is still lacking in embryos of 20 mm. ; it separates from the musculus rectus superior, probably from its medial border; in fetuses of 60 mm. it lies medial tc that muscle and in those of 75 mm. it overlaps its medial edge. At the end of the fourth month it has acquired its definitive position above the superior rectus.

In conclusion some statements may be made concerning the growth of the eye and the eye of the new-born child, this latter having a quite different structure from that of the adult (Merkel and Orr, 1892). The portion from the entrance of the optic nerve to the fovea centralis is completely formed at this time, but the more anterior portions of the bulbus lag decidedly behind in their growth. The cornea, it is true, is relatively large (compare also Greef, 1892), but, on the other hand, the ciliary body is small and must grow much more rapidly than the cornea in order to attain its definitive size. The lens enlarges only in its equatorial diameter, its axis actually becoming smaller. The region of most distinct vision remains stationary, but the medial portion of the bulb enlarges in general more than the lateral, and the cornea and lens are accordingly pushed laterally until their central points, which were at first situated medially, come to lie in the opti<' axis that passes through the fovea centralis. The physiological excavation of the papilla is present in the new-born child (compare also Hippel, 1898). Fig. 202 gives a representation of the points mentioned; it shows a diagrammatic section of the eye of a new-born child enlarged five diameters. The contours of the adult eye.

File:Keibel Mall 2 202.jpg

Fig. 202. Schematic section of the eye of a new-born child, enlarged five times. The contours of an adult eye, when lens is accommodated for near vision, have been reduced to the size of that of the new-born hild and are represented in red. (After Merkel and Orr. 1892.) whose lens is accommodated for near vision, have been reduced to the size of the eye of the new-born and are represented in red. To the right a ciliary process is shown, to the left a depression between two ciliary processes. According to Hippel, the wall -like thickened margin of the fovea centralis is not yet formed in the new-born child and the shining reflection at the periphery of the fovea is not seen with the ophthalmoscope, but in children of four weeks a thickening can be perceived. The fibres of the optic nerve are never myelinated at birth, but become so at about the tenth week after birth. 24 Weiss (1894, 1895, 1897) found that the eye after birth increased in weight 3.25 fold, while the entire weight cf the body increased 21 times. The increase in the volume of the eye is about 3.29 times. The correspondence of the increase of the eye with that of the brain, which is about 3.76 times, is striking, and the growth of the eye and that of the brain are completed earlier than that of the rest of the body. Of the diameters of the eye the vertical (with reference to the position of the eye in the body) is that which increases most rapidly, while the sagittal one, which is the greatest at birth, shows the least increase; as a result, the shape of the eye becomes almost spherical in children of nine years, and later the vertical diameter exceeds the sagittal. As may be seen from the relations of the eye muscles, the sclera grows almost equally in both its distal and proximal portions. For further data concerning the growth of the eye, in addition to the authors alreadv mentioned, the following may be consulted : Dieekmann (1896), "Duclos (1895), Halben "(1900), 0. Lange (1901), Baratz (1902), and Hippel (1898 2 ).

  • Held (1896) showed that in animals born with the eyes closed the stimulus of light hastened the development of the myelination.


(On the development of the eye.)

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Corking, H. : Ueber die Entwicklung der Kopf- und Extremitat-muskulatur. Morphol. Jahrb. Vol. 28, p. 28-104, with 4 plates. 1899.

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Recherches sur le developpement de la membrane pupillaire cbez l'homme. Arch. d'Ophthalm. Vol. 30, pp. 4S0-498, with 8 figs. 1910.

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Dewecker, L.: Das Weinen und die Triinen der Neugeborenen. Klin. Monatsbl. fur Augenheilk. Vol. 38, p. 220-226. 1899.

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Dieckhann : Beitrage zur Anatomie und Physiologie des neugeborenen Auges. Inaug. Diss. Marburg. Pp. 41. 1896.

Dryault, A. : Appareil de la vision. In Poirier and Charpy, Traite d'anatomie humaine. Vol. 5, p. 1018. 1904.

Duclos, J. : Etude sur les dimensions du cristallin. Thesis. Bordeaux 1895. Van Duyse: Elements d'embryologie et teratologie de l'oeil. Paris 1904.

Elze, C. : Beschreibung eines menschlichen Embryo von ca. 7 mm. gr. L. Anat. Hefte. Vol. 35, Heft 106. 1908.

Falchi, F. : Sur l'histogenese de la retine et du nerf optique. Arch. ital. de biol. Vol. 9, p. 382-399, with 1 plate. 1888

Ueber die Histogenese des retina und des nervus opticus. Grafe's Arch. fiir Ophthalm. Vol. 34, Part 2, p. 67-108, with 3 plates. 1888
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Fritz, W. : Ueber die membrana Descemetii und das ligamentum pectinatum iridis bei den Saugetieren und beim Menschen. Sitzber. k. k. Akad. Wiss. Wien. Math-naturwiss. Kl. Vol. 115. With 3 plates. 1906.

Froriep, A.: Ueber die Entwicklung des Sehnerven. Anat. Anz. Vol. 6. 1891. Ueber die Einstiilpung der Au^enblase. Arch, fiir mikr. Anat. Vol. 66. 1905

Die Entwicklung des Auges der Wirbeltiere. In Hertwig's Handbuch. Vol. ii, 2, p. 244. 1905 2 .
Ueber die Herleitung des Wirbeltierauges vom Auge der Ascidienlarve. Verh. Anat. Gesellsch. (Rostock 1906.) Anat. Anz. Suppl. Vol. 29. 1906.

Fuchs, H. : Zur Entwicklungsgeschichte des Wirbeltierauges. I. Ueber die Entwicklung der Augengefiisse des Kaninchens. Anat. Hefte. Vol. 28, Heft 84, p. 1-251, 194-216. 1905.

Gabri elides, A. : Recherches sur l'embryogenie et de 1' anatomic comparee de Tangle de la chambre anterieure chez le poulet et cbez l'homme. Muscle dilatateur de la pupille. Thesis. Paris 1895 \ The same in : Arch, d'ophthalrn. Vol. 15, p. 176-193. 1895 \

Goez, A. : Untersuchung von Tranendrusen aus verschiedenen Lebensaltern. Med. Diss. Tubingen 1908.

Greet, R. : Studien iiber die Plastik des menschlichen Auges am Lebenden und den Bildwerken des Antike. Arch, fiir Anat. und Physiol. Anat. Abth. P. 113-136. 1892.

Grynfeltt, E. : Sur le developpement du muscle dilatateur de la pupille chez le lapin. Comptes Rend. Acad. Sci. Paris. Vol. 127, p. 966-968. 1898 \ Le muscle de la pupille chez les mammiferes. Thesis for Doctorate in Medicine. Montpellier. Pp. 106, with 5 plates. 1898 2 .

Haemers, A. : Regeneration du corps vitre. Arch, d'ophthalrn. Vol. 23, p. 103 114. 1903.

Halben, R. : In welchem Verhaltnis wachst das mensehliche Auge von der Geburt bis zur Pubertal. 1 plate. Med. Diss. Breslau. 1900.

Heerfordt, C. : Studien iiber den musculus dilator pupillae, samt Angabe von gemeiuschafthchen Kennzeichen einiger Falle eipthelialer Muskidatur. Anat. Hefte. Vol. 14, Heft 46, p. 487-558, with 7 plates. 1900 \ Berichtigung zum Aufsatze iiber den musculus dilatator pupillae, etc. Ibid. Vol. 15, Heft 49, p. 721. 1900 \

Held, H. : Beitrag zur Kenntnis des Nervenmarks. 3. Ueber experinientelle Reifung des Nervenmarks. Arch, fiir Anat. und Physiol. Anat. Abth., p. 222-229. 1896.

Henckel, Fr. : Beitrage zur Entwicklungsgeschichte des menschlichen Auges. Anat. Hefte. Vol. 10, Heft 33, p. 485-510, with 2 plates. 1898. Also as Med. Dissert. Giessen. 1898.

Herr, F. : Beitrag zur Entwicklungsgeschichte des menschlichen Auges. Med. Diss. Berlin. 1893.

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Hochstetter, F. : Bilder der ausseren Korperf orm einiger menschlicher Embiyonen. Munich 1908.

Hoffmann, C. : Beitrage zur Entwicklungsgeschichte der Selachii. Part I. 4 plates. Morphol. Jahrb. Vol. 24. 1896. Part 2. 2 plates. Ibid. Vol. 25, p. 248-304. 1897.

Jacobi, E.: Ueber die Neuroglia des Sehnerven. Klin. Monatsbl. fiir Augenheilk. Vol. 43, p. 129-137, with 4 plates. 1905.

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Johnston, J. B. : The Morphology of the Vertebrate Head from the Viewpoint of the Functional Divisions of the Nervous System. Journ. Comp. Neurol. and Psychol. Vol. 15, p. 175-275, with 4 plates. 1905.

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Studien zur Entwicklungsgeschichte des Schweines. Schwalbe's Morphol. Arbeiten. Vol. 5, p. 17-168. 1895.

Keibel F. Normal Plates of the Development of the Pig Embryo (Sus scrofa domesticus). (1897) Vol. 1 in series by Keibel F. Normal plates of the development of vertebrates (Normentafeln zur Entwicklungsgeschichte der Wirbelthiere) Fisher, Jena., Germany.

Die aussere Korperform und der EntwiekluBgsgrad der Organe bei Affen einbryonen. 9th part of Selenka's Menschenaffen. Wiesbaden 1906 \ Die Entwicklungsgeschichte des Wirbeltierauges. Klin. Monatsbl. fiir Augenheilk. Vol. 44. New series. Vol. 2, p. 112-132. 1906

Keibel F. and Elze C. Normal Plates of the Development of the Human Embryo (Homo sapiens). (1908) Vol. 8 in series by Keibel F. Normal plates of the development of vertebrates (Normentafeln zur Entwicklungsgeschichte der Wirbelthiere) Fisher, Jena., Germany.

Keil, R. : Beitrage zur Entwicklungsgeschichte des Auges vom Schwein, mit besnderer Berucksichtigung des Verhaltens der fetalen Augenspalte. Anat. Hefte. Vol. 32, Heft 96. 1906.

Kessler, L. : Zur Entwieklung des Auges der Wirbeltiere. Leipzig 1897.

Kirchsteix, F. : Ueber die Tranendriise des Neugeborenen und die Unterschiede derselben von der des Erwachsenen. Med. Diss. Berlin 1894.

Knape, V.: Ueber die Entwieklung der Hornhaut der Hiibnchens. Anat. Anz.Vol. 34, p. 417-424. 1909.

Kolliker, A. von : Ueber die Entwieklung und Bedeutung des Glaskorpers. Verh. Anat. Gesellseh. 17. Vers. Anat. Anz. Suppl. Vol. 23, p. 49-51. 1903.

Die Entwieklung und Bedeutung der Glaskorpers. Zeitschr. fiir wiss. Zool. Vol. 76, p. 1-25. 1904.

Konigstein, L. : Histologische Notizen. Arch, f iir Ophthalm. Vol.30. 1884.

Kollmann, J.: Lehrbuch der Entwicklungsgeschichte des Menschen. Jena 1898.

Krueckmaxn, E. : Ueber die Entwieklung und Ausbildung der Stiitzsubstanz im Sehnerven und in der Netzhaut. 5 plates. Klin. Monatsbl. fiir Augenheilk. Vol. 44. New series. Vol. 1, p. 162-191. 1906.

Lang, P.: Zur Entwieklung der Tranenausfuhrapparates beim Menschen. Anat. Anzeiger. Bd. 38, pp. 561-569. 1911.

Lange, O. : Zur Anatomie des Auges des Neugeborenen. 1. Zur Anatomie des Ciliarmuskels der Neugeborenen. Klin. Monatsbl. fiir Augenheilk. Vol. 39, p. 1-6. 1901. 2. Suprackorioidealraum. zonula Zinnii, ora serrata mid sogenannte physiologische Exkavation der Sehnervenpapille. Ibid., p. 202-213. 1901. Einblicke in die embryonale Anatomie unci Entwieklung des Mensehenauges.

Nach ei^enen Praparaten dargestellt. With atlas of 33 plates. Wiesbaden 1908.

Leber, Th. : Die Zirkulations- und Ernahrungsverhaltnisse des Auges. In Grafe-Samisch's Handbuch der gesamten Augenheilkunde. 2d ed. Vol. 2. 2. 1908. Published 1903. Legal. E. : Zur Entwicklungsgeschichte des Tranennasenganges bei Siiugetieren. Med. Diss. Breslau 1881.

Die Nasenhdhlen und der Tranennasengang der amnioten Wirbeltiere. IV. Morphol. Jahrb. Vol. 8, p. 353-372. 18S3. (Compare Born, 18S3.)

Lenhossek, M. : Die Entwieklung des Glaskorpers. Leipzig 1903.

Die Entwieklung und Bedeutung der zonula ciliaris. Verkandl. anat. Gesellsch. (1911)! Erg.-Heft Anat. Anzeiger. Bd. 38, pp. 81-88. 1911.

Lewis, W. H. : Experimental Studies on the Development of the Eye in Amphibia.

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Lubosch, W. : Besprechung einen neuen Theorie der Licht- und Farbenempfindung nebst einem Exkurs iiber die stammesgeschichtliche Entstehung des Wirbeltierauges. Morphol. Jahrb. Vol. 39, p. 146-153. 1909.

Magitot, A. : Etude sur le developpement de la retine humaine. Ann. d'Oculistique. Vol. 143, p. 241. 1910. Matts, V. : Die Entwieklung der Tranenableitungswege. Zeitsehr. fur Augenheilk. Vol. 14, p. 222-246, with 1 plate. 1905. Part 2. Ibid. Vol. 16, p. 303 314, with 3 plates. 1906.

Merkel, Fr., and Orr, A. : Das Auge des Neugeborenen an einem sehematischen Durchschnitt erlautert. Anat. Hefte. Vol. 1, Heft 3, p. 271-299. 1892. Minot, C. S.: Human Embryology. New York 1S92.

Monesi, L. : Die Morphologie der fetalen Tranenwege beim Mensehen. 10 plates. Klin. Monatsbl. fur Augenheilk. Jahrg. 42. Vol. 1, p. 1-37. 1904.

Neal, H. : The Segmentation of the Nervous System in Squalus acanthias. Bull. Mus. Comp. Zool., Harvard College, with 9 plates. Vol. 31. 1897. The Problem of the Vertebrate Head. Journ. Comp. Neurol. Vol. 8. 1898.

Nussbaum, M. : Nerv und Muskel. 1. Mitteilung. Arch, fiir mikr. Anat. Vol. 37, p. 416-446, with 1 plate. 1896. Entwieklung der Augenmuskeln bei den Wirbeltieren. Sitzber. niederrhein. Ges. fiir Natur- und Heilkunde. Bonn 1S99. Entwicklungsgeschichte des mensehlichen Auges. In Grafe-Samisch's Handbuch der gesamten Augenheilk. 2d ed. Part 15, p. 35-39. 1900. (Published in Part I of Vol. 2 in 1908.)

Oppel, A. : Ueber Vorderkopfsomiten und die Kopfhohle von Anguis f ragilis. Arch, fur mikr. Anat. Vol. 36. 1890. Van Pee, P. : Recherches sur l'origine du corps vitre. Arch, de Biol. Vol. 19, p. 317-385. 1903.

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Rabl, C. : Ueber den Bau und die Entwieklung der Linse. 1. Selachier und Amphibien. Zeitsehr. fiir wiss. Zool. Vol. 63. 1898. 2. Reptilien und Vogel. Ibid. Vol. 65. 1899. 3. Saugetiere. Riiekblick und Sehluss. Ibid. Vol. 67. 1900. Ueber den Bau und Entwieklung der Linse. Leipzig 1900. Zur Frage naeh der Entwieklung des Glaskorpers. Anat. Anz. Vol. 22. 1903.

Ramon y Cajal, S. : Nouvelle contributions a l'etude histologique de la retine, etc. Journ. de lAnat. et de la physiol. Vol. 32. 1896.

Retzius, G. : Ueber den Bau des Glaskorpers und der zonula Zinnii in dem Auge des Mensehen und einiger Tiere. Biolog. Untei-sueh. N. S. Vol. 6. 1894.

Reuter, K. : Ueber die Entwieklung der Augenmuskulatur beim Sehwein. Anat. Hefte. Vol. 9, p. 365. with 2 plates. 1897. (Also as Inaug. Diss. Gottingen. Pp. 21, with 1 plate. 1897.

Rex, H. : Ueber das Mesoderm des Vorderkopfes der Ente. Arch, fur mikr. Anat. Vol. 50. 1897.

Riquier, G. C. : Contributo alio studio della ghiandola lacrimale umana. Monit. Zool. Ital. Vol. 22, pp. 56-65, with 1 plate. 1911.

Schon, W. : Zonula und ora serrata. Anat. Anz. Vol. 10, p. 360-364. 1895 \ Der Uebergangsraum der Netzhaut oder die sogenannte ora serrata. Arch, f iir Anat. u. Entwicklungsgesch. P. 417-422, with 1 plate. 1895 2 .

Schultze, 0. : Zur Entwicklungsgeschichte des Gefasssystems im Saugetierauge. Kollikeris Festschrift. Leipzig 1892. Ueber die Entwicklung und Bedeutung der ora serrata des menschlichen Auges. Verh. Phys.-nied. Gesellsch. Wiirzburg. Xew series. Vol. 34. 1902. Schweigger-Seidel : Anatomisehe Mitteilungen. Virchow's Arch. Vol. 37. 1866.

Seefelder, R. : Nochmals zur Frage der Netzhautanomalien in sonst normalen fetalen menschlichen Augen. Arch. f. Ophthahn. Bd. 79. 1911.

Seefelder and Wolfrum : Zur Entwicklung der vorderen Kammer und des Kammerwinkels beim Menschen, nebst Bemerkungen iiber ihre Entstehung bei Tieren. Arch, fur Ophthalm. Vol. 63, p. 430-451, with 2 plates. 1906.

Seiler, H. : Zur Entw. des Konjunktivalsackes. Arch, f iir Anat. u. Physiol. 1S90.

Sewertzoff, A. : Die Entwicklung der Occipitalregion der niederen Vertebraten in Zusammenhang mit der Frage nach der Metamerie des Kopfes. Bull. Soc. Nat. Moscou. 1895. Studien zur Entwicklung des Wirbeltierkopfes. 2. Die Metamerie des Kopfes des elektrisehen Rochen. Ibid. 1898.

Spampani, G. : Alcune richerche sull'origine et la nature del vitreo. Monit. Zool. Ital. Anno 12, p. 145-153, with 1 plate. 1901. Speciale-Cirincione : Sullo sviluppo della glandola lacrimale nell'uomo. Naples. V. Pasquale. 1908 \ Ueber die Entw. der Tranendriise beim Menschen. Arch. f. Ophth. Vol. 69. 1908*.

Spemann, H. : Ueber Correlationen in der Entwicklung des Auges. Verh. anat. Gesellsch. 15 Vers. Bonn. Anat. Anz. Vol. 19, Suppl., p. 61-79. 1901. Ueber eine neue Methode der embryonalen Transplantation. Verh. Deutsch. Zool. Gesellsch. 18 Vers. Marburg. P. 195-202. 1906. Strahl, H. : Zur Entw. des menschlichen Auges. Anat. Anz. Vol. 14. 1898.

Szely, A. : Zur Anatomie und Entwicklungsgeschichte der hinteren Irisschichten, mit besonderer Berucksichtigung des musculus sphincter iridis beim Menschen. Anat. Anz. Vol. 20, p. 161-175. 1902 \ Beitrag zur Kenntnis der Anatomie und Entwicklungsgeschichte der hinteren Irisschichten, mit besonderer Berucksichtigung des musculus sphincter pupillae des Menschen. Arch, fur Ophthalm. Vol. 53. 1902 s . Zur Glaskorperfrage. Anat. Anz. Vol. 24, p. 417-428. 1904. Ein nach unten und innen gerichtetes, nicht mit der Fetalspalte zusammenhangendes Kolobom der beiden Augenbecher, bei einem etwa vier Wochen alten menschlichen Embryo. Klin. Monatsbl. fiir Augenheilk. Vol. 45, Suppl., p. 201-219. 1907. Ueber das Entstehen eines fibrillaren Stutzgewebes im Embryo und dessen Verhaltnis zur Glaskorperfrage. Anat. Hefte. Vol. 35, Heft 107. 1908. Ueber die Entstehung der melanot. Pigmentes im Auge der Wirbeltierembryonen und in Choroi'dealsarkomen. Arch, fiir mikr. Anat. Bd. 7. 1911.

Tornatola, S. : Origine et nature du corps vitre. Resume of communication made to 12th Internat. Congress of Med., Moscow. 1897. Ricerche embriologiche sull'occhio dei vertebrati. Atti della R. Accad. Peloritana. Vol. 13. 1898.

Ucke, A. : Zur Entw. des Pigmentepithels der retina. St. Petersburg. 1891.

Versari, R. : Morf ologia dei vasi sanguigni arteriosi dell' occhio dell' uomo e di altri mammiferi. Ric. fatte nel laborat di auat. norm, della R. universita di Roma et in altri laborat. Vol. 5, p. 181-234. 1900 \ Contributa alia conoscenza della morfogenese degli strati vascolari della coroide nelP occhio dell' uorno e di altri mammiferi. Ibid. Vol. S, p. 5-31. 1900 s . Abstract in Arch. Ital. de Biol. Vol. 36, p. 356-357. 1901. La morfogenesi dei vasi sanguigni della retina umana. Ibid. Vol. 10, p. 1-38. 1903. Abstract in Arch. Ital. de Biol. Vol. 41, p. 482-485. 1904. Ueber die Entwicklung der Blutgefasse des menschlichen Auges. Anat. Anz. Vol. 35, p. 105-109. 1909.

Virchow, H. : Facher, Zapf en, Leiste, Polster, Gef asse im Glaskorperraum von Wirbeltieren, sowie damit in Verbindung stehende Fragen. Ergebnisse Anat. unci Entwicklungsgesch. Vol. 10, p. 720-844. 1901. Voll, A. : Ueber die Entwicklung der membrana vasculosa retinae. Kolliker's Festschrift, gewidmet vom anat. Institut zu Wiirzburg. 1892.

Vossius, A. : Beitrage zur Anatomie des nervus opticus. Arch, f iir Ophthalm. Vol. 29, Part 4, p. 119-150. 1883.

Weiss, L. : Ueber das Verhalten des musculus rectus extemus und rectus internus bei wacksender Divergenz der orbita. Arch, fur Augenheilk. Vol. 29, p. 29S-323, with 3 plates and 3 text figs. 1S94. Das Wachstum des Auges. Report of the 24th meeting of the Ophthalm. Society, Heidelberg, 1895. Extra Suppl. of Klin. Monatsbl. fiir Augenheilk. Vol. 33, p. 218-224. 1895. Ueber das Wachstum der menschlichen Auges und liber die Veranderung der Muskelinsertionen am wachsenden Auge. Anat. Hefte. Vol. 8, Heft 25, p. 191-248, with 3 plates and 2 text plates. 1897.

Van Wijhe, J. : Ueber die Mesodermseg-mente und die Entwicklung der Nerven der Selachierkopfes. Verh. Konigl. Akad. Wiss. Amsterdam. 1882 \ Ueber das Visceralskelett und die Nerven des Kopfes der Ganoiden und von Ceratodus. Niederl. Arch, fur Zool. Vol. 5. 1882 \ Wolfrum : Zur Genese der Glaskorpers. Report of the 33d meeting of the Ophthalm. Soc, Heidelberg, 1906. Wiesbaden 1907.

Zimmermann, K. : Ueber Kopfhohlenrudimente beim Menschen. Arch, fiir mikr. Anat. Vol. 53, p. 481-484. 189S.

Zumstein and Osaki : Report of the 29th meeting of the Ophthalm. Soc, Heidelberg. P. 220. 1901 \ Compare also Zumstein, Modelle zur Entwicklung des Auges. Marburger Sitzber. P. 54-59. 1901 2 .

   Manual of Human Embryology II 1912: Nervous System | Chromaffin Organs and Suprarenal Bodies | Sense-Organs | Digestive Tract and Respiration | Vascular System | Urinogenital Organs | Figures 2 | Manual of Human Embryology 1 | Figures 1 | Manual of Human Embryology 2 | Figures 2 | Franz Keibel | Franklin Mall | Embryology History
  1. Compare, on this point, F. Keibel (1906 ! ) and the recent works of Brachet (1907 \ 1907 ") and Lubosch (1909).