Embryology of the Eye Neuroepithelium Lens Placode Prosencephalon

Embryology of the Eye Neuroepithelium Lens Placode Prosencephalon [diencephalon] Optic Vesicle Mandibular Arch A B View B Med 6573: Nervous System University of Minnesota Medical School Duluth Donna J. Forbes, Ph. D. 29 February 2008

References Moore & Persaud, Chapter 19, pages 492 - 503 Nolte: Chapter 17, pages 411 - 412 Dr. Downing’s “Histology of the Eye”

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

Critical Period for Development of the Eyes Middle of Week 4 to Middle of Week 8, but continues to birth

Neuroepithelium [AKA Neuroectoderm] Neuroectoderm of the Prosencephalon [diencephalon] (Diencephalon) Lens Placode Optic Vesicle Optic Grooves Mandibular Arch Optic Vesicles Optic Cups • Retina • Optic Nerve • Ciliary Body • Iris

Eye Development Optic Grooves Optic Vesicles ≈22 days Optic Cups Neuroepithelium Prosencephalon [diencephalon] ≈28 days Lens Placode Optic Vesicle Mandibular Arch ≈32 days M & P 19 - 1

Eye Development Optic Nerve, Optic or Choroid Fissure & Lens ≈22 days Neuroepithelium Prosencephalon [diencephalon] ≈28 days Lens Placode Optic Vesicle Mandibular Arch ≈32 days M & P 19 - 1

Eye Development Optic Nerve & Optic or Choroid Fissure cont. ≈22 days Neuroepithelium Next slide Prosencephalon [diencephalon] ≈28 days Lens Placode Optic Vesicle Mandibular Arch ≈32 days M & P 19 - 1

Closure of the Optic Fissure & Formation of the Optic Nerve • Optic Fissure • Pupil • Hyaloid vessels • Optic Nerve (ON) • Sheath of ON Edges of the pupil M & P 19 - 3

Retina, Ciliary Body, Iris, Lens Mesenchyme The following slides look at each of these derivatives. M & P 19 - 8

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 Intraretinal space • Inner layer of optic cup >> neural layer of retina. • Intraretinal Space B A Hyaloid artery of retina Neural layer of the retina Mesenchyme Pigment epithelium of the retina C Central artery of retina • Ora Serrata = junction of neural retina with ciliary Ora serrata located body. about here • Hyaloid artery & vein >> Central artery & vein of retina. D Note: Intraretinal space is eliminated by fusion of the pigment layer with the neural layer of the retina.

Retina Outer layer of optic cup Optic Cup Mesenchyme Lens Pit Optic Vesicle Lens Vesicle Diencephalon Inner layer of optic cup Intraretinal space 3. 5 wks 4 wks Neural layer of the retina Lens 6 wks Lens 6. 5 wks Lens Pigment epithelium layer of the retina 8 wks

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

Ciliary Body [= processes + muscle] From mesenchyme e me m chy sen Anterior chamber Primary (posterior) lens fibers Posterior chamber Ciliary epithelium [pigmented & non-pigmented 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.

Iris e ym nch ese m From neuroectoderm Anterior chamber Primary (posterior) lens fibers Anterior lens fibers Posterior chamber 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.

Differentiation of the Lens Lumen within the Lens Vesicle Mesenchyme Lens Pit Optic Vesicle Diencephalon Area of the Lens Placode 3. 5 wks Anterior layer of the Lens 5 wks 4 wks Lens Remnants of hyaloid vessels Posterior layer of the Lens 6 wks 6. 5 wks Note that lumen disappears 8 wks

Aqueous Chambers & Vitreous Body Mesenchyme Future Anterior chamber [aqueous humor] Irido-pupillary membrane Posterior chamber [aqueous humor] Irido-pupillary membrane Anterior chamber [aqueous humor] Central artery of retina Hyaloid artery Vitreous body Hyaloid canal

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.

Cornea & Conjunctiva Mesenchyme Surface Ectoderm 3 layers of the cornea Epithelium Stroma Endothelium 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.

Cornea Epithelium Stroma Endothelium

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: ü Skeletal muscle ü Orbicularis oculi (2 nd arch; facial, SVE) ü Levator palpebrae superioris (pre-otic myotomes; oculomotor, GSE) ü Smooth muscle ü Superior tarsal (mesenchyme; sympathetics, GVE) Eyelids re-opened by ~26 wks.

Congenital Cataract Balloon-Like Congenital Cataract Lens becomes opaque during intrauterine life. Etiologies: • Rubella infection of mom at 4 - 7 wks gestation • Hereditary • Malnutrition • Chromosomal abnormalities • Radiation • Galactosemia Congenital Familial Central Cataract

Detached 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.

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

Congenital Coloboma 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