1. University of Minnesota Medical School Duluth
Embryology of the Eye
View B
Prosencephalon
Neuroepithelium
Optic Vesicle B
[diencephalon]
Lens Placode
Mandibular Arch A
Note: There is NOT an accompanying .doc file.
VIEW B is a coronal slice indicated by the red line in VIEW A.
Med 6573: Nervous System
University of Minnesota Medical School Duluth
Donna J. Forbes, Ph.D.
29 February 2008

2. References
Moore & Persaud, Chapter 19, pages Nolte: Chapter 17, pages Dr. Downing’s “Histology of the Eye”

3. Learning Objectives
Optic Cup: Relationship to diencephalon & to lens placode during development
Origin and Formation of the:
Optic Nerve & Retina
Iris & Ciliary Body
Lens
Choroid, Sclera & Cornea
Inductive influences involved in the development of the eye.
Congenital malformations of the eye

4. Critical Period for Development of the Eyes
The most critical period of eye development is weeks 4 to 8, but further development continues until birth. Myelination of the optic nerve continues after birth.
Middle of Week 4 to Middle of Week 8, but continues to birth

5. Neuroectoderm of the Prosencephalon
Neuroepithelium
Lens Placode
Optic Vesicle
Mandibular Arch
[diencephalon]
[AKA Neuroectoderm]
Neuroectoderm of the Prosencephalon
(Diencephalon) 
Optic Grooves 
Optic Vesicles 
Retina
Optic Nerve
Ciliary Body
Iris
--OPTIC VESICLES grow out laterally from the DIENCEPHALON. The cavity of each optic vesicle is continuous with the ventricular cavity of the diencephalon.
--The surface ectoderm will give rise to:
------LENS PLACODE from which the LENS will develop
------EPITHELIUM of the CORNEA.
Optic Cups

6. Eye Development Optic Grooves Optic Vesicles Optic Cups
≈22 days
Prosencephalon
Neuroepithelium
Lens Placode
Optic Vesicle
Mandibular Arch
[diencephalon]
≈28 days
--OPTIC GROOVES (OR SULCI) appear early in week 4, when the cranial neuropore is still open.
--During Week 5, the OPTIC VESICLES fold in on themselves to form the OPTIC CUPS. They become double-walled with an outer and an inner layer separated by the INTRARETINAL SPACE
≈32 days
M & P

7. Optic Nerve, Optic or Choroid Fissure & Lens
Eye Development
Optic Nerve, Optic or Choroid Fissure & Lens
≈22 days
Prosencephalon
Neuroepithelium
Lens Placode
Optic Vesicle
Mandibular Arch
[diencephalon]
≈28 days
--The proximal portion of the optic vesicle becomes constricted to form the OPTIC STALK which differentiates into the OPTIC NERVE.
--Remember that the optic nerve is a fiber tract of the diencephalic portion of the brain.
--The OPTIC OR CHOROID FISSURE is a linear indentation on the ventral aspect of the developing optic cup and optic stalk. The blood vessels travel in this fissure.
--The Optic Vesicles induce the surface ectoderm to form the LENS PLACODE. It acquires a depression or LENS PIT which enlarges to form the LENS VESICLE. The lens vesicle pinches off from the surface ectoderm as the LENS is formed. (more later)
≈32 days
M & P

8. Optic Nerve & Optic or Choroid Fissure cont.
Eye Development
Optic Nerve & Optic or Choroid Fissure cont.
≈22 days
Prosencephalon
Neuroepithelium
Lens Placode
Optic Vesicle
Mandibular Arch
[diencephalon]
Next slide
≈28 days
≈32 days
M & P

9. Closure of the Optic Fissure & Formation of the Optic Nerve
Pupil
Hyaloid vessels
Optic Nerve (ON)
Sheath of ON
OPTIC OR CHOROID FISSURE gradually closes leaving a round opening facing the developing lens, i.e. the PUPIL of the eye.
--Note that the space within the optic fissure is NOT in communication with the lumen of the optic stalk.
--The optic fissure is in the inferior nasal aspect of the developing eye.
--HYALOID ARTERY & VEIN become enclosed within the closing optic fissure and form the CENTRAL ARTERY & VEIN OF THE RETINA. These vessels supply the inner layer of the optic cup and during development they supply the posterior layer of the lens vesicle.
OPTIC NERVE composed of the axons of the ganglion cell layer of the neural retina (and, therefore, the inner layer of the optic cup); travel toward the diencephalon in the inner layer of the optic stalk. As these axons proliferate, they obliterate the lumen of the optic stalk. Central artery and vein of the retina end up in the center of the optic nerve.
--SHEATH OF THE OPTIC NERVE forms from surrounding mesenchyme. It is continuous with the meninges of the brain and the choroid/sclera of the eye. Increased intracranial pressure leads to swelling of the optic disc, i.e. PAPILLEDEMA, because of the continuity of these ensheathing membranes.
--Myelination of the optic nerve: incomplete at birth, so it takes awhile for a newborn to really see their visual world. What cells form the myelin of the optic nerve? Why is it important to know that?
Edges of the pupil
M & P

10. The following slides look at each of these derivatives.
Retina, Ciliary Body, Iris, Lens
Mesenchyme
The following slides look at each of these derivatives.
Retina, Ciliary Body and Iris develop from the neuroectoderm of the optic cup.
Lens develops from surface ectoderm.
M & P

11. Retina: forms from the two layers of the optic cup
Developing pigment epithelium of the retina [from outer layer of optic cup]
Developing neural layer of the retina [from inner layer of optic cup]
Outer layer of optic cup >> pigment layer of retina
Inner layer of optic cup >> neural layer of retina.
Intraretinal Space
Ora Serrata = junction of neural retina with ciliary body.
Hyaloid artery & vein >> Central artery & vein of retina.
Intraretinal space
Hyaloid artery of retina A B C D
Ora serrata located about here
Neural layer of the retina
Mesenchyme
Pigment epithelium of the retina
OUTER LAYER OF THE OPTIC CUP: Cells acquire melanin pigment granules. This developing layer has a strong inductive influence on the development of the neural retina, choroid and sclera.
INNER LAYER OF THE OPTIC CUP forms the complex layers of the NEURAL retina, i.e. rods, cones, bipolar cells, ganglion cells, etc.
INTRARETINAL SPACE is located between the outer and inner layers of the developing retina. Disappears as the outer and inner layers of the developing retina fuse with one another. DETACHED RETINA is due to separation of the attachment between the neural and pigment layers of the retina as the result of trauma, for example.
HYALOID ARTERY & VEIN form the CENTRAL ARTERY and VEIN OF THE RETINA. These vessels supply the inner layer of the optic cup and during development they supply the posterior layer of the lens vesicle. The portion of these vessels that lies within the vitreous regresses during fetal life (“D” in this slide) since the lens will become avascular in the adult.
Central artery of retina
Note: Intraretinal space is eliminated by fusion of the pigment layer with the neural layer of the retina.

12. Retina
Outer layer of optic cup
Optic Cup
Mesenchyme
Lens Vesicle
Lens Pit
Optic Vesicle
Diencephalon
Intraretinal space
Inner layer of optic cup
3.5 wks
4 wks
5 wks
Neural layer of the retina
--Review the relationship of the optic vesicle to the developing layers of the retina.
--Note that in “F”, the space between the neural and pigment layers of the retina is an artifact of preparing the specimen.
--Lens development covered in a later slide.
Lens
Lens
Lens
Pigment epithelium layer of the retina
6 wks
6.5 wks
8 wks

13. Ora serrata located about here
Ciliary Body & Iris
Develop from the inner & outer layers of the optic cup -- anterior to the ora serrata.
Mesenchyme
Lens A B
Ora serrata located about here
Ciliary Body
Iris
NEXT SLIDE
Iris
Central artery of retina C D

14. Ciliary Body [= processes + muscle]
From mesenchyme
mesenchyme
Ciliary epithelium [pigmented & non-pigmented
Anterior chamber
Primary (posterior) lens fibers
Posterior chamber
Anterior lens fibers
Pigmented & non-pigmented layers of ciliary epithelium that cover the ciliary processes develop from the outer & inner layers, respectively, of the optic cup.
Ciliary muscle (smooth muscle) develops from surrounding mesenchyme.

15. Primary (posterior) lens fibers
Iris
mesenchyme
From neuroectoderm
Anterior chamber
Primary (posterior) lens fibers
Posterior chamber
EPITHELIAL LAYER grows inward or medially and partially covers the lens. It is located on the posterior aspect of the iris, facing the posterior chamber.
--Two cell layers thick since it is formed by the rostral continuation of the inner, non-pigmented and the outer, pigmented layers of the ciliary body & retina.
--Pigment forms in these cell layers; bluish in most infants; adult eye will be blue if pigment is confined to these epithelial layers.
STROMAL OR CONNECTIVE TISSUE LAYER is located on the anterior aspect of the iris, facing the anterior chamber.
--Pigment in this layer imparts brown color to iris; the greater the amount of pigment in this layer, the “browner” the eye will appear.
--SPHINCTER & DILATOR MUSCLES OF THE IRIS develop in this layer. While these are smooth muscles, they develop from the neuroectoderm of the optic cup. [This is an EXCEPTION to the general rule that muscles develop from mesoderm.]
Anterior lens fibers
STROMAL LAYER OF IRIS
Epithelial layer forms from the most rostral aspect of optic cup; 2 cell layers thick; posterior side of iris; blue pigment
Stromal or connective tissue layer forms from mesenchyme; anterior side of iris; brown pigment
Sphincter & Dilator muscles of the pupil develop within the stromal layer of the iris from neuroectoderm of the optic cup.

16. Differentiation of the Lens
3.5 wks
4 wks
5 wks
6 wks
6.5 wks
8 wks
Differentiation of the Lens
Lumen within the Lens Vesicle
Mesenchyme
Lens Pit
Diencephalon
Optic Vesicle
Area of the Lens Placode
Anterior layer of the Lens
LENS PLACODE  LENS PIT  LENS VESICLE  LENS
--LENS: While the LENS PLACODES are not yet obvious in “A”, it is the INDUCTIVE INFLUENCE of the Optic Vesicles contacting the surface ectoderm that causes the LENS PLACODES to form.
--ANTERIOR LAYER OF THE LENS VESICLE remains thin and forms the SUBCAPSULAR LENS EPITHELIUM on the anterior surface of the lens.
--POSTERIOR LAYER OF THE LENS VESICLE gives rise to the PRIMARY LENS FIBERS which elongate to fill (and eliminate) the LUMEN of the vesicle.
--Primary lens fibers lose their nuclei and must last a lifetime.
--Lens epithelial cells in the equatorial zone (or outer rim of the lens) serve as a stem cell population from which new SECONDARY LENS FIBERS are formed throughout life; these secondary lens fibers are added to the lateral aspects of the primary fibers.
NOTE: the lens is AVASCULAR in the adult; it depends upon diffusion from the aqueous humor. Note the remnants of the hyaloid vessels in “D” and “E”.
Lens
Lens
Note that lumen disappears
Remnants of hyaloid vessels
Posteriorlayer of the Lens

17. Aqueous Chambers & Vitreous Body
Mesenchyme
Future Anterior chamber
Anterior chamber
[aqueous humor]
Irido-pupillary membrane
Posterior chamber
[aqueous humor]
--ANTERIOR CHAMBER appears as a space in the mesenchyme between the developing lens and cornea. It becomes filled with aqueous humor that is secreted by the ciliary processes.
--POSTERIOR CHAMBER forms as a space in the mesenchyme posterior to the developing iris and anterior to the developing lens. It is filled with aqueous humor that is secreted by the ciliary processes.
--VITREOUS BODY is transparent and gelatinous; it differentiates from mesenchyme lying between the lens and retina.
--HYALOID CANAL: Hyaloid vessels that pass through the vitreous early in development to supply the posterior aspect of the lens vesicle, regress during fetal life, leaving behind the ‘hyaloid canal’.
Hyaloid canal
Hyaloid artery
Vitreous body
Central artery of retina

18. Vascular plexus of the choroid layer Sheath of the optic nerve
Choroid & Sclera
Mesenchyme
Vascular plexus of the choroid layer
Sclera
Sheath of the optic nerve
Choroid and Sclera form from surrounding mesenchyme.
Inner layer is the vascular & pigmented CHOROID. Comparable to pia-arachnoid.
Outer layer is the tough SCLERA. Comparable to dura. Continuous with the sheath of the optic nerve, posteriorly.

19. Cornea & Conjunctiva
3 layers of the cornea
Mesenchyme
Surface Ectoderm
Epithelium
Stroma
Endothelium
-Epithelium of the cornea is continuous peripherally with the conjunctival epithelium which covers the sclera (or “white” of the eye).
Three layers of the cornea & conjunctiva form at the most anterior aspect of the eye.
SURFACE ECTODERM induced by lens to form the EPITHELIUM of the cornea & conjunctivum.
STROMA is derived from mesenchyme.
ENDOTHELIUM forms from the mesenchymal lining of the anteior chamber.

20. Cornea
Epithelium
Stroma
Endothelium

21. Eyelids re-opened by ~26 wks.
Mesenchyme
Eyelids
Surface Ectoderm
Eyelids fused by Wk 10
Transverse folds of surface ectoderm + mesenchyme begin to form in Week 6.
Muscles & Nerves of the Eyelids:
Skeletal muscle
Orbicularis oculi (2nd arch; facial, SVE)
Levator palpebrae superioris (pre-otic myotomes; oculomotor, GSE)
Smooth muscle
Superior tarsal (mesenchyme; sympathetics, GVE)
Eyelids re-opened by ~26 wks.

22. Congenital Cataract Lens becomes opaque during intrauterine life.
Balloon-Like Congenital Cataract
Lens becomes opaque during intrauterine life.
Recall the TRIAD of Rubella associated congenital defects involving the eye (congential cataract), ear (deafness) and cardiac defects.
Etiologies:
Rubella infection of mom at wks gestation
Hereditary
Malnutrition
Chromosomal abnormalities
Radiation
Galactosemia
Congenital Familial Central Cataract

23. Detached Retina
Iris of right eye
Retina
Iris of right eye
Disruption of the adhesion between the neural and pigmented layers of the retina.
These examples in the adult.
During development, congenital detached retina appears to be:
due to failure of the retinal layers to fuse and obliterate the intraretinal space.
caused by unequal growth of the eye.

24. Congenital Ptosis
Iris of right eye
Retina A B
Disturbed development of the levator palpebrae superioris and/or its oculomotor (GSE) innervation.
Surgically corrected
Autosomal dominant trait
Iris of right eye

25. Congenital Coloboma Defective closure of the choroid or optic fissure
Retina of right eye
Iris of right eye
Defective closure of the choroid or optic fissure
Position: infero-nasal quadrant reflective of the location of the optic fissure during development
Iris of right eye
Usually seen only in the iris (Coloboma iridis) but can extend into the ciliary body, retina, choroid and optic nerve.
Iris of right eye