Talk:2009 Lecture 19

From Embryology

UNSW Embryology - Eye


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.


Related Pages: [eye2.htm Vision Abnormalities] | [eye11.htm Vision Molecular] | [week4_3.htm Week 4 - Sensory Placodes] | [head.htm Head Notes] | [face.htm Face Notes] | [neuron.htm Neural Notes]

Some Recent Findings

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."


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.

# Inner limiting membrane - Müller cell footplates.
  1. Nerve fiber layer - retinal ganglion axons eventually the optic nerve.
  2. Ganglion cell layer - neuronal cell bodies of retinal ganglion cells, their axons form the nerve fiber layer and eventually the optic nerve.
  3. Inner plexiform layer - another layer of neuronal processes.
  4. Inner nuclear layer - neuronal cell bodies
  5. Outer plexiform layer - another layer of neuronal processes.
  6. Outer nuclear layer - neuronal cell bodies
  7. External limiting membrane - layer separating inner segment portions of photoreceptors from their cell nuclei.
  8. Photoreceptor layer - rods and cones that convert light into signals.
  9. Retinal pigment epithelium.

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


  • Human Embryology (2nd ed.) Larson Ch12: p375-409
  • The Developing Human: Clinically Oriented Embryology (6th ed.) Moore and Persaud Ch19: p491-511
  • Essentials of Human Embryology Larson Ch12: p252-272
  • Before We Are Born (5th ed.) Moore and Persaud Ch20: p460-479
  • Human Embryology, Fitzgerald and Fitzgerald
  • Search PubMed- Medline

Computer Activities

UNSW Embryology:

Science Lecture (2004) Slides:

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.htm Class Notes] page.

Lecture Slides [../Sections/anat2310/2004/ANAT2310L4Eyes1.pdf Lecture 04 Vision (1 Slide / Page for Viewing)] | [../Sections/anat2310/2004/ANAT2310L4Eyes4.pdf Lecture 04 Vision (4 Slides / Page for Printing)] (educational use only)

Embryo Images Unit:

Embryo Images Online - Eye Development

Weeks 3-4Eye Fields-Optic Vesicle

Weeks 5-6Optic Cup, Lens Vesicle, Choroid Fissure, Hyaloid Artery

Weeks 7-8 Cornea, Anterior Chamber, Pupillary Membrane, Lens, Retina

Weeks 9-15 Iris, Ciliary Body

Weeks 8-10 Eyelids

Development Timing

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)


Developmental Overview

Developmental Genes

Pax6 active in epithelial and mesenchymal cells during ocular development (at different times). (More? [#15950457 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 [#17021046 Bras-Pereira C, Bessa J, Casares F., 2006])

Components of Eye Formation

[#surface ectoderm surface ectoderm] | [#neural crest neural crest] | [#neural ectoderm neural ectoderm] | [#blood vessels blood vessels] | [#perioptic mesoderm perioptic mesoderm] | [#hyaloid cavity hyaloid cavity]

surface ectoderm

lens placode

lens pit

lens vesicle

lens fibres

lens capsule

embryonic/fetal nucleus

eyelid(inner canthus)

conjunctival sac

conjunctival sac (upper & lower recesses)

tear ducts

optic eminence

corneal ectoderm

cornea (+neural crest)


neural crest

perioptic mesenchyme


ectoderm (endothelium of anterior chamber)

Descemet membrane (from stroma and ectoderm)

cornea (+surface ectoderm)

scleral mesenchyme


[#table top of table]

neural ectoderm

optic placode & optic sulcus

optic pit

optic vesicle (primary)

optic vesicle (secondary)

future pigment layer

pigment layer

future neural layer

neural layer

nerve fibre layer

inner nuclear layer

intermediate nuclear layer

outer nuclear layer

ciliary body (from retinal periphery)

iris (pupil)

optic stalk

optic nerve (II) optic chiasma

optic disc

choroid/fetal fissure

[#table top of table]

blood vessels

internal carotid artery

opthalmic artery

hyaloid vascular plexus

choroidal vessels

tunica vasculosa lentis

hyaloid artery (central artery of retina)

vasa hyaloidea propria

[#table top of table]

perioptic (orbital) mesoderm

extrinsic ocular muscles PMM

extrinisic ocular muscles

[#table top of table]

hyaloid cavity

anterior chamber

vitreous humour

Modified from The Anatomical Basis of Mouse Development Kaufman and Bard, 1999 Academic Press

Retinotopic Map

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.

Links: Neuroscience - The Retinotopic Representation of the Visual Field | MCB - Retinotopic map in the chick | MBOC4 - Neuronal Specificity Guides the Formation of Orderly Neural Maps

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? [week4_3.htm#eye 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).

surface ectoderm -> lens placode -> lens pit -> lens vesicle -> lens fibres -> lens capsule and embryonic/fetal nucleus.

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 PubMed

Search Jan 2009 "eye development" 39,222 reference articles of which 4,841 were reviews.

Search PubMed: term = embryonic eye development | eye development | retina development

Older Recent Findings

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."

Internal Links Vision

Vision[eye2.htm Vision Abnormalities][eye11.htm Vision Molecular]

Senses[senses2.htm#abnormal Senses Abnormalities][senses2.htm#OMIM OMIM][senses2.htm#Questions Questions][senses2.htm#PubMed Medline][senses3.htm#Pig Pig Stage 13/14][senses4.htm#Human Human (Stage22)][senses5.htm Selected Human highpower][ear.htm Hearing][ear2.htm Hearing Abnormalities][sensestxt.htm Text only page][senseslink.htm WWW Links]