Clinical embryology and development of the eye

Chapter 2 Clinical embryology and development of the eye

This chapter deals with the embryology of the eye. We concentrate on organogenesis of the globe and then examine the differentiation of the components of the eye and provide the anatomical substrate for developmental ocular conditions.

The vertebrate eye is formed through coordinated interactions between neuroepithelium, surface ectoderm, and extraocular mesenchyme.1 The neuroectoderm gives rise to the retina, iris, and optic nerve; the surface ectoderm forms the lens and corneal epithelium; the extraocular mesenchyme comprising mesodermal and neural crest cells gives rise to the corneal stroma, corneal endothelium, extraocular muscles, and fibrous and vascular coats of the eye.2

Three main periods can be distinguished in the prenatal development of the eye:

Table 2.1 Overview of eye development4

Gestational age Developmental milestone
22 days Optic primordia appears
2nd month Hyaloid artery fills embryonic fissure
  Closure of embryonic fissure begins
  Lid folds appear
  Neural crest cells (corneal endothelium) migrate centrally; corneal stroma follows
  Choroidal vasculature starts to develop
  Axons from ganglion cells migrate to optic nerve
3rd month Sclera condenses
  Lid folds meet and fuse
4th month Retinal vessels grow into nerve fiber layer near optic disc
  Schlemm’s canal appears
  Glands and cilia develop in lids
5th month Photoreceptors develop inner segments
  Lids begin to separate
6th month Dilator muscle of iris forms
7th month Central fovea thins
  Fibrous lamina cribrosa forms
  Choroidal melanocytes produce pigment
8th month Iris sphincter develops
  Chamber angle completes formation
  Hyaloid vessels regress
  Retinal vessels reach periphery
  Myelination of optic nerve fibers is complete to lamina cribrosa
  Pupillary membrane disappears

Eye organogenesis (4th–8th week gestation human)

Fourth week

In the fourth week, the optic pits deepen and form the optic vesicles (OVs) which are evaginations of the lateral walls of the diencephalon. The OVs are connected to the forebrain by the optic stalk (a short tube that eventually forms the optic nerve) (Fig. 2.1A). Interaction between the OV and surface ectoderm (SE) induces the lens placode, and the wall of the OV in contact with the SE thickens to form the retinal disk. Towards the end of the fourth week invagination begins to transform the OV into the optic cup (OC). Simultaneously, the primordia of the extraocular muscles appear as condensations in the periocular mesenchyme. Disruptions in these early steps lead to severe congenital anomalies, including anophthalmia, microphthalmia, and optic fissure closure defects (coloboma).5,6

Fifth week

The process of invagination of the OV to form the OC predominates in the fifth week. Invagination involves the retinal disk, lens plate, and the ventrocaudal wall of the OV (Fig. 2.1B). Invagination of the retinal disk of the OV leads to formation of the inner layer of the OC which becomes the neural retina, while the external layer of the OC will become the retinal pigment epithelium (RPE) (Fig. 2.1C). The OC is not continuous, and forms a fold inferiorly and ventrally that is continuous with the optic stalk. This fold, called the embryonic (optic) fissure (Fig. 2.3), allows the passage of the hyaloid artery into the OC. The primary vitreous develops around the hyaloid vasculature. The process of invagination also involves the lens placode (plate), which leads to the formation of the lens pit. The lens pit deepens to become the lens vesicle. Further development leads to the lens vesicle separating from the SE.7 The lens vesicle is large and fills the OC.8 The SE becomes the corneal epithelium (Fig. 2.1D).1,3

Eighth week

In the eighth week, there is marked development of the optic nerve as ganglion cells differentiate; by the end of this week, 2.67 million axons have formed. Optic nerve axons start to make contact with the brain and establish a rudimentary chiasm.11 The RPE nears maturation with the appearance of melanosomes. Müller cells appear now and extend radial fibers inwards to form the internal limiting membrane and outward toward the future external limiting membrane.

Corneal differentiation includes endothelial cells starting to form Descemet’s membrane; the corneal stroma consists of 5–8 rows of cells and the corneal epithelium is evolving to a stratified squamous epithelium.

The lens develops rapidly during this period. The primary lens fibers fill the lens vesicle. The intracellular organelles disappear. The equatorial epithelial cells begin to divide and new cells are pushed posteriorly, then elongate and become the secondary lens fibers. With the formation of the secondary lens fibers, there is development of the lens bow which represents the nuclei of the secondary lens fibers. They form an arc with a forward convexity (Fig. 2.1E). The lens “sutures” develop where the secondary lens fibers meet in a linear pattern at the anterior and posterior poles of the lens. The sutures initially are in a Y shape anteriorly and an inverted Y (image) posteriorly.7,12

The four rectus muscles insert into the sphenoid bone and the trochlea develops. The lacrimal glands form from the superotemporal quadrant of the conjunctival sac.

Differentiation and maturation of elements


The cornea’s main function as a transparent “window” derives from its unique structure and composition permitting the transmission and refraction of light.13 It consists of three layers: an outer epithelial layer, a middle stromal layer consisting of a collagen-rich ECM interspersed with keratocytes, and an inner endothelial cell layer.

The corneal epithelium develops from SE and its maturation is related to eyelid development. Rudimentary lids fuse 8 weeks after ovulation and do not separate until 26 weeks.14 Bowman’s membrane, which underlies the corneal epithelium, develops from the processes of superficial mesenchymal stromal cells. It first becomes apparent around week 16 and is easily recognizable by the fifth month.15

The beginnings of the corneoscleral junction, which will become the limbus, appear at the end of the eighth week. This is marked by a change in stromal appearance at the periphery of the cornea, with cells acquiring a more polymorphic shape and losing regular orientation. By week 11, this junction is well demarcated. In place of the limbal folds identifiable in adult corneas, a ridge-like structure circumscribes and demarcates the developing cornea. This represents the primitive corneal epithelial stem cell niche.15

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Jun 4, 2016 | Posted by in OPHTHALMOLOGY | Comments Off on Clinical embryology and development of the eye
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