This chapter follows the chapters describing the globe and orbit because the study of embryology can be difficult if the adult structure, organization, and function of the eye are not known. Although studying the development of a structure after studying the structure itself might seem backward, in my experience this has proved to be a useful sequence for the student. In this chapter, the development of each structure is described separately, but the reader must keep in mind that these events are occurring simultaneously.

With the explosion of information from improved technology and human genome study, new information is reported daily about the processes that control cellular development, structure, and function. A number of growth factors have been identified that bind to receptor sites on target cells to control normal development by modulating proliferation, migration, and differentiation.1 These processes are at the basis of structure development. Cells from germ layers migrate to a specific location and then proliferate, forming the population of cells that will differentiate into the specific cell type necessary.

D E V E L O P M E N T O F

O C U L A R S T R U C T U R E S

By the third week of embryonic development, the three primary germ layers—ectoderm, mesoderm, and endo- derm—have formed the embryonic plate.2 (Of these three, only ectoderm and mesoderm will take part in the developing ocular structures.) A thickening in the ectoderm, visible on the dorsal surface of the embryo, forms the neural plate, which will give rise to the central nervous system, including ocular structures. A groove forms down the center of this plate at approximately day 18 of gestation, and the ridges bordering the groove grow into neural folds. As the groove expands, these folds grow toward one another and fuse to form the neural tube along the dorsal aspect of the embryo. Just before fusing, an area of cells on the crest of each of the neural folds separates from the ectoderm; these are neural crest cells. They form islands of cells within the mesoderm, which now surrounds the neural tube. The neural tube is formed on or near day 22.2 The tissue of the neural tube is now called neural ectoderm and the

surface layer is now called surface ectoderm. Neural and surface ectoderm differ in anatomic location and in differentiation potentials (Box 7-1). Figure 7-1 illustrates these events.

OPTIC PITS

Indentations form in the inner surface of the neural tube on both sides of the forebrain region even before the tube is completely closed. These indentations are the optic pits. On approximately day 25, after the neural tube has closed, the optic pits expand forming lateral sac-shaped extensions, the optic vesicles.3 The cavity within the optic vesicle is continuous with the lumen of the neural tube. The surface of each vesicle expands until it comes in contact with surface ectoderm then

▲BOX 7-1

Embryologic Derivation of Ocular Structures

Surface ectoderm gives rise to:

•Lens

•Corneal epithelium

•Conjunctival epithelium

•Epithelium of eyelids and cilia, meibomian glands, and glands of Zeis and Moll

•Epithelium lining nasolacrimal system

Neural ectoderm gives rise to:

•Retinal pigment epithelium

•Neural retina

•Optic nerve fibers

•Neuroglia

•Epithelium of ciliary body

•Epithelium of iris

•Iris sphincter and dilator muscles Neural crest gives rise to:

•Corneal stroma (which gives rise to Bowman’s layer)

•Corneal endothelium (which gives rise to Descemet’s membrane)

•Most (or all) of sclera

•Trabecular structures

•Uveal pigment cells

•Uveal connective tissue

•Ciliary muscle

•Meninges of optic nerve

•Vascular pericytes

A

C

Neural folds

D

E

G

gradually becomes separated from it by cells of neural crest origin and mesoderm.4

Neural crest cells and mesoderm collectively make up the mesenchyme, from which the connective tissue of the globe and orbit develop. Although most orbital connective tissue is derived from neural crest, determining whether a structure is of neural crest or mesodermal origin sometimes is difficult because mesodermal cells and neural crest cells appear similar cytologically.5 If the origin is uncertain, mesenchyme is cited as the germ layer.

As the optic vesicle evaginates, the tissue joining the vesicle to the neural tube constricts, forming the optic stalk (Figure 7-2). The cells lining the inner surface of this entire formation are ciliated, and the outer surface is covered by a thin basal lamina.3 The cavity of the optic stalk, as well as that of the optic vesicle, is continuous with the space that will become the third ventricle.

While the wall of the optic vesicle is in contact with surface ectoderm, it thickens and flattens to form the retinal disc.5 The lower wall of the optic vesicle and optic stalk begins to buckle and move inward toward the upper and posterior walls. This invagination forms a cleft, variously called the optic fissure, embryonic fissure, or fetal fissure. (It has also been called the “choroidal fissure,” but this name will be avoided because it may imply that the choroid is involved in the fissure, which it is not.) The inferior wall continues to move inward, pulling the anterior wall of the optic vesicle with it and placing the retinal disc in the approximate location of the future retina. The edges of the fissure grow toward one another and begin to fuse at 5 weeks; fusion starts at the center and proceeds anteriorly toward the rim of the optic cup and posteriorly along the optic stalk. Closure is complete at 7 weeks, forming the two layers of the optic cup and optic stalk6 (Figure 7-3). Mesenchyme enters the fissure and moves into the cavity of the developing optic cup.

FIGURE 7-1

Formation of neural tube.  A, Dorsal surface of embryo as seen from above. B, Horizontal section through three-layered embryonic disc. C, Neural groove forms in neural plate area of ectoderm. D, Neural groove invaginates, and neural folds are formed. E, Neural folds continue to grow toward each other. F, Neural crest cells separate from ectoderm of neural folds as the folds fuse; neural tube is formed (of neural ectoderm); and surface ectoderm is again continuous. G, Evaginations in area of forebrain form the optic pits.

Optic groove

Level of section B

Neural fold

Neural groove

A

Neural tube

Notochord

Forebrain

Mesenchyme

Lens placode

Optic vesicle

C

Mesenchyme

Midbrain

Surface ectoderm

Forebrain

Lumen of optic stalk

Mesenchyme

Hyaloid artery

DEarly stage of optic cup

Outer layer of optic cup

Inner layer of optic cup

Lens vesicle

Optic fissure

Hyaloid artery

F Hyaloid veinLevel of section G

Hyaloid artery

Lens vesicle

Wall of brain

Intraretinal space

H

Lens

Hyaloid vessels

in optic fissure

Lumen of optic stalk

Inner layer of optic stalk (containing axons of ganglion cells)

Mesenchyme

B

C

Hyaloid vessels in optic fissure

C

Lens

Optic fissure closed

Level of section D

Ganglion cell layer of the retina

Axons of ganglion cells

Optic stalk

Lens

Walls of optic stalk continuous with the wall of the brain and the layers of the optic cup

Axons of ganglion cells

Hyaloid vessels

Sheath of the optic nerve (continuous with the meninges of the brain and the choroid and sclera)

Central artery and

vein of the retina