These notes introduce the development of the eye: induction and regional specification of the eye structures, maturation and formation of retina and optic tectum neuronal connections.
Early embryonic eye: optic vesicle and lens placode
Late embryonic eye: cornea, lens, retina, optic stalk, extraocular muscles
Page Links: Introduction | Some Recent Findings | stage 13/14 embryo | stage 22 embryo | stage 22 embryo highpower | Retina | Reading | Computer Activities | Objectives | Science Lecture (2004) Slides | Development Timing | Development Overview | Components of Eye Formation | Retinotopic Map | Developmental Genes | References | Glossary
Teraoka ME, Paschaki M, Muta Y, Ladher RK. Rostral paraxial mesoderm regulates refinement of the eye field through the bone morphogenetic protein (BMP) pathway.
Dev Biol. 2009 Apr 9. [Epub ahead of print] PMID: 19362544
"The eye field is initially a large single domain at the anterior end of the neural plate and is the first indication of optic potential in the vertebrate embryo. ...Here we describe a role for the rostral cephalic paraxial mesoderm in limiting the extent of the eye field. The anterior transposition of this mesoderm or its ablation disrupted normal development of the eye. Importantly, perturbation of optic vesicle development occurred in the absence of any detectable changes in the pattern of neighbouring regions of the neural tube. Furthermore, negative regulation of eye development is a property unique to the rostral paraxial mesoderm. The rostral paraxial mesoderm expresses members of the bone morphogenetic protein (BMP) family of signalling molecules and manipulation of endogenous BMP signalling resulted in abnormalities of the early optic primordia."
Embryo (stage 13) showing the optic vesicles and lens placode. These Carnegie stage 13/14 6mm (CRL) pig embryo sections are approximately equal to day 42 Human Embryo.
Embryo (stage 22) showing eye structures
(anterior chamber, lens, posterior chamber, retina, optic nerve, nasolacrimal duct, extraocular muscles)
The Carnegie stage 22 Human Embryo is 27mm (CRL) in size and approximately equal to day 54 - 56 of development.
Embryo (stage 22) showing detailed selected regions (shown in blue boxes) of the eye covering optic nerve, retina (neural and pigmented) and lens.
The Carnegie stage 22 Human Embryo is 27mm (CRL) in size and approximately equal to day 54 - 56 of development.
Vertebrates have ten identifiable layers formed from neurons, their processes (nerve fibers), membranes, photoreceptors and pigmented cells. Light must pass through nearly all these layers to the photoreceptors.
Historic Retina image (Cajal)
Developmental Biology (6th ed.) Gilbert, Scott F. Sunderland (MA): Sinauer Associates, Inc.; c2000. Development of the Vertebrate Eye
Molecular Biology of the Cell (4th ed.) Alberts, Bruce; Johnson, Alexander; Lewis, Julian; Raff, Martin; Roberts, Keith; Walter, Peter. New York: Garland Publishing; 2002. The Formation of an Entire Organ Can Be Triggered by a Single Gene Regulatory Protein | Sensory Epithelia
Neuroscience (2nd ed.) Purves, Dale; Augustine, George.J.; Fitzpatrick, David; Katz, Lawrence.C.; LaMantia, Anthony-Samuel.; McNamara, James.O.; Williams, S. Mark, editors. Sunderland (MA): Sinauer Associates, Inc. 2001 Critical Periods in Visual System Development | Figure 11.3. Development of the human eye | Effects of Visual Deprivation on Ocular Dominance |
Genes and disease Bethesda (MD): National Library of Medicine (US), NCBI. Diseases of the Eye
These links are to PDF versions Vision Development slides from the 2004 Science lecture series. The first link is 1 Slide / Page for Viewing only. The second link is 4 Slides / Page for Printing. These documents are also linked from the Class Notes page.
Embryo Images Unit:
Weeks 3-4 Eye Fields-Optic Vesicle
Weeks 9-15 Iris, Ciliary Body
Weeks 8-10 Eyelids
Week 3 - beginning of "eye fields" of neural tube at the level of the proencephalon.
Week 4 - optic sulci form as indentations at the level of the diencephalon which extend towards and then contact the surface ectoderm.
Week 5 -
Week 9 -
Week 12-16 -
Week 16-24 -
3rd Trimester -
(These are Human embryonic timings, not clinical which is based on last menstral period +2 weeks)
Pax6 active in epithelial and mesenchymal cells during ocular development (at different times). (More? Pax6 Review)
Pitx2 homeobox gene: in neural crest required for optic stalk and ocular anterior segment development.
Rx paired-like homeobox gene
odd-skipped in drosophila, expressed at posterior margin of eye field and is required to activate hedgehog expression signaling onset of retinogenesis.
Hh Hedgehog trigger for retina development in drosophila.
EGF Epidermal Growth Factor receptor signaling pathway: roles in cell proliferation, survival and differentiation.
FGF Fibroblast growth factors: retinal cell proliferation, retinal ganglion cell axon guidance/target recognition, craniofacial patterning and lens induction.
TH Thyroid Hormone: cone photoreceptor development and differentiation.
Dach1 homologue of drosophila dachshund, encoding a nuclear protein, and expressed in eye during early development.
Drosophila: Pax6 specifies eye primordium then hedgehog (hh) signals decapentaplegic (Dpp/Bmp4) which is produced by surrounding posterior margin cells (see Bras-Pereira C, Bessa J, Casares F., 2006)
Modified from The Anatomical Basis of Mouse Development Kaufman and Bard, 1999 Academic Press
This neuroscience term describes how the developing retina is precisely "mapped" onto the visual cortex through a series of signaling and activity dependent mechanisms. This follows from Hubel and Wiesel (1981 Nobel Prize in Physiology or Medicine) key discoveries (1959-70) of how in development system matching occurs in the visual system. The topographic map establishes an ordered neuronal connection between sensory structures and the central nervous system.
The retinotectal map (eye to brain) of birds (lower vertebrates):
temporal (posterior) retina is connected to the rostral (anterior) part of the contralateral optic tectum
nasal (anterior) retina to the caudal (posterior) tectum
ventral retina to the dorsal (medial) tectum
dorsal ventral (lateral) tectum
retinal waves a form of coordinated spontaneous activity that occurs in the developing retina. These waves of electrical activity (action potentials) are thought to have a role in establishing the initial retinotopic map by correlating/coordinating the activity of neighbouring retinal ganglion cells.
EphA/ephrin-A molecular signaling also thought to have a role in establishing the initial retinotopic map.
References: Hubel DH, Wiesel TN. Ferrier lecture. Functional architecture of macaque monkey visual cortex. Proc R Soc Lond B Biol Sci. 1977 Jul 28;198(1130):1-59. | Torborg CL, Feller MB. Spontaneous patterned retinal activity and the refinement of retinal projections. Prog Neurobiol. 2005 Jul;76(4):213-35. | McLaughlin T, O'Leary DD. Molecular gradients and development of retinotopic maps. Annu Rev Neurosci. 2005;28:327-55. | Nicol X, Voyatzis S, Muzerelle A, Narboux-Neme N, Sudhof TC, Miles R, Gaspar P. cAMP oscillations and retinal activity are permissive for ephrin signaling during the establishment of the retinotopic map. Nat Neurosci. 2007 Jan 28;
The lens or crystalline lens or aquula (Latin, aquula = a little stream) has a key role in focussing light (with the cornea) upon the neural retina. The lens embryonic origin is from surface ectoderm of the sensory placodes that form in the head region (More? Week 4 - Placodes). The lens focusses by refracting light as it passes through the biconvex lens, which can be altered in shape (accommodation) by surrounding ciliary muscles. These ciliary muscles are activated (contracted) by parasympathetic innervation from the ciliary ganglion itself innervated by the oculomotor nerve (Cranial Nerve III) (More? Cranial Nerves).
A recent paper has characterised, by weight analysis, growth of the human lens.
Growth of the lens: in vitro observations. Augusteyn RC. Clin Exp Optom. 2008 May;91(3):226-39. Epub 2008 Mar 6. Review.
"Human lens growth differs from growth in other species in that it occurs in two distinct modes. The first follows a sigmoidal relationship and provides an initial burst of rapid growth during prenatal development with an apparent termination at or shortly after birth. The second growth mode is linear, adding 1.38 mg/year to lens wet weight, throughout life."
Kozmik Z. Pax genes in eye development and evolution. Curr Opin Genet Dev. 2005 Aug;15(4):430-8.
Lukats A, Szabo A, Rohlich P, Vigh B, Szel A. Photopigment coexpression in mammals: comparative and developmental aspects. Histol Histopathol. 2005 Apr;20(2):551-74.
Collinson JM, Hill RE, West JD. Analysis of mouse eye development with chimeras and mosaics. Int J Dev Biol. 2004;48(8-9):793-804.
Amato MA, Boy S, Perron M. Hedgehog signaling in vertebrate eye development: a growing puzzle. Cell Mol Life Sci. 2004 Apr;61(7-8):899-910.
Cvekl A, Tamm ER. Anterior eye development and ocular mesenchyme: new insights from mouse models and human diseases. Bioessays. 2004 Apr;26(4):374-86.
Gehring WJ. The genetic control of eye development and its implications for the evolution of the various eye-types. Int J Dev Biol. 2002 Jan;46(1):65-73.
Chow RL, Lang RA. Early eye development in vertebrates. Annu Rev Cell Dev Biol. 2001;17:255-96.
Bras-Pereira C, Bessa J, Casares F. Odd-skipped genes specify the signaling center that triggers retinogenesis in Drosophila. Development. 2006 Oct 4
Evans AL, Gage PJ. Expression of the homeobox gene Pitx2 in neural crest is required for optic stalk and ocular anterior segment development. Hum Mol Genet. 2005 Nov 15;14(22):3347-59.
Search Jan 2009 "eye development" 39,222 reference articles of which 4,841 were reviews.
Ambati BK, etal. Corneal avascularity is due to soluble VEGF receptor-1. "Corneal avascularity, the absence of blood vessels in the cornea, is required for optical clarity and optimal vision, and has led to the cornea being widely used for validating pro- and anti-angiogenic therapeutic strategies for many disorders. ...Manatees, the only known creatures uniformly to have vascularized corneas, do not express sflt-1, whereas the avascular corneas of dugongs, also members of the order Sirenia, elephants, the closest extant terrestrial phylogenetic relatives of manatees, and other marine mammals (dolphins and whales) contain sflt-1, indicating that it has a crucial, evolutionarily conserved role."
Williams SE, Grumet M, Colman DR, Henkemeyer M, Mason CA, Sakurai T. A role for Nr-CAM in the patterning of binocular visual pathways. Neuron. 2006 May 18;50(4):535-47. "cell adhesion molecule Nr-CAM is expressed by RGCs that project contralaterally and is critical for the guidance of late-born retinal ganglion cells (RGCs) within the ventrotemporal crescent. Blocking Nr-CAM function causes an increase in the size of the ipsilateral projection and reduces neurite outgrowth on chiasm cells in an age- and region-specific manner. Finally, we demonstrate that EphB1/ephrin-B2-mediated repulsion and Nr-CAM-mediated attraction comprise distinct molecular programs that each contributes to the proper formation of binocular visual pathways."
Roberts MR, Srinivas M, Forrest D, Morreale de Escobar G, Reh TA. Making the gradient: Thyroid hormone regulates cone opsin expression in the developing mouse retina. Proc Natl Acad Sci U S A. 2006 Apr 10 "Most mammals have two types of cone photoreceptors, which contain either medium wavelength (M) or short wavelength (S) opsin. ...Thyroid hormone (TH) is symmetrically distributed in the retina at birth as S-opsin expression begins, but becomes elevated in the dorsal retina at the time of M-opsin onset (postnatal day 10). ...Suggest that the ratio and patterning of cone types may be determined by TH availability during retinal development."
Evans AL, Gage PJ. Expression of the homeobox gene Pitx2 in neural crest is required for optic stalk and ocular anterior segment development. Hum Mol Genet. 2005 Nov 15;14(22):3347-59. "Heterozygous mutations in the homeobox gene, PITX2, result in ocular anterior segment defects and a high incidence of early-onset glaucoma."
retina - The stratified sensory structure of the eye, formed from the neural ectoderm that extends from the forebrain (diencephalon) to form initially the folded optic cup. Vertebrates have ten identifiable layers formed from nerve fibers, neurons, membranes, photoreceptors and pigmented cells. Light must pass through nearly all these layers to the photoreceptors. (1. Inner limiting membrane - Müller cell footplates; 2. Nerve fiber layer; 3. Ganglion cell layer - layer of retinal ganglion cells their axons form the nerve fiber layer and eventually the optic nerve; 4. Inner plexiform layer - another layer of neuronal processes; 5. Inner nuclear layer; 6. Outer plexiform layer; 7. Outer nuclear layer; 8. External limiting membrane - layer separating inner segment portions of photoreceptors from their cell nuclei; 9. Photoreceptor layer - rods and cones that convert light into signals; 10. Retinal pigment epithelium).
retinal pigment epithelium - (RPE) An epethial pigmented cell layer lying outside the sensory retina, formed from the outer layer of the folded optic cup. The RPE is firmly attached to the underlying choroid and overlying retinal visual cells, for which it has a nutritional role.
retinal waves - A form of coordinated spontaneous activity that occurs in the developing retina. These waves of electrical activity (action potentials) along with EphA/ephrin-A signaling are thought to have a role in establishing the initial retinotopic map by correlating/coordinating the activity of neighbouring retinal ganglion cells.