The neural retina develops from the invagination of the inner aspect of the optic cup, and the RPE develops from the outer layer. The apposed surfaces of these 2 layers are ciliated. The inner-layer cilia go on to form photoreceptors, while the outer-layer cilia regress. Although the physical space between these layers eventually closes, it remains a potential space; retinal detachments occur when fluid accumulates, due to various etiologies, within this space.
Neural (inner) retinal development is driven by overlapping cascades of genetic programs; several “master” switches help determine lineages and drive cell fate, such as Nrl (neural retina leucine zipper), a transcription factor of the Maf subfamily that serves as an intrinsic regulator of rod photoreceptor development. Retinal development occurs concentrically, beginning in the center of the optic cup and extending peripherally. Lamination of the neural retina occurs at approximately 8–12 weeks of gestation with the formation of inner and outer neuroblastic layers. Ganglion cells appear to be the first to differentiate; early in the second trimester, they proliferate rapidly (Fig 4-9). The internal and external limiting membranes form when cells cease to proliferate and begin to differentiate.
Retinal vasculature develops from remnants of the hyaloid artery; this artery is retained within the optic nerve and eventually becomes the central retinal artery (Fig 4-10). Endothelial cells organize posteriorly, with vessel development following the same concentric pattern as retinal development (this is the basis for zones I–III [location of involvement] in the classification of retinopathy of prematurity).
Figure 4-9 Development of the neural retina. The inner neuroblastic layer (INBL) gives rise to ganglion, Müller, and amacrine cells. The outer neuroblastic layer (ONBL) gives rise to bipolar and horizontal cells. Later, the cell bodies and outer segments of the photoreceptors develop. GCL = ganglion cell layer; ILM = internal limiting membrane; INL = inner nuclear layer; NFL = nerve fiber layer; ONL = outer nuclear layer; OPL = outer plexiform layer; RPE = retinal pigment epithelium; TLC = transient layer of Chievitz.
(Reproduced with permission from Forrester JV, Dick AD, McMenamin PG, Roberts F, Pearlman E. The Eye: Basic Sciences in Practice. 4th ed. Edinburgh: Elsevier; 2016:115.)
Figure 4-10 Development of the optic nerve. The hyaloid artery enters the eye via the embryonic fissure. As the fissure closes, the artery is retained within the optic nerve stalk and becomes the central retinal artery. Condensation of the surrounding neural crest cells and mesoderm form the optic nerve sheath and pial vessels. The developing ganglion cells grow toward the optic nerve stalk along the inner layer of ectoderm. The outer layer will form the lamina cribrosa. Astroglia generate the septae around the nerve bundles. These cells later give rise to oligodendrocytes, which myelinate the postlaminar axons of the retinal ganglion cells.
(Modified with permission from Forrester JV, Dick AD, McMenamin PG, Roberts F, Pearlman E. The Eye: Basic Sciences in Practice. 4th ed. Edinburgh: Elsevier; 2016:117.)
Retinal pigment epithelium
The RPE forms from proliferating pseudostratified columnar epithelial cells that create lateral tight junctions and deposit a basement membrane, which later becomes the inner layer of the Bruch membrane. The RPE is the only pigmented tissue in the body that is not derived from neural crest cells, although these cells are located at the anterior-most edge of the neural crest, suggesting shared origins.
The optic nerve develops from the optic stalk, the narrow stalk that connects the optic vesicle with the forebrain (see Fig 4-6B, C). The optic stalk is highly active in regulating cell migration into and around the developing eye, mostly through release of ligands and expression of growth factor receptors. It initially forms from neuroectodermal cells surrounded by neural crest cells. In the sixth week of gestation, neuroectodermal cells begin to vacuolate and degenerate, providing space for axons from the ganglion cells of the inner retina (see Fig 4-10). The surrounding neural crest cells form meninges, whereas neuroectodermal cells form surrounding oligodendrocytes (to form myelin sheaths). Peripheral nerves, including most cranial nerves, are surrounded by myelin supplied by Schwann cells. The exception is the optic nerve, which is surrounded by oligodendrocytes. This difference is an important reason for the optic nerve’s susceptibility to neuritis.
The vitreous is probably formed from both mesodermal and ectodermal components: Neural crest cells of the inner optic cup probably contribute the connective fibers of the vitreous. The hyaloid vasculature develops from mesodermally derived cells (Fig 4-11; see also Fig 4-6C, D, and Fig 4-10). The primary vitreous, the earliest vitreous in the embryo, forms a central conical structure that contains the hyaloid vasculature (Fig 4-12) and is surrounded by secondary vitreous. The secondary vitreous forms from hyalocytes as the primary vitreous begins to regress, eventually (by the sixth fetal month) enveloping the regressed primary vitreous. Between months 4 and 6, the zonular fibers of the lens develop from tertiary vitreous and are distinct from the primary and secondary vitreous. Remnants of the primary vitreous include the Cloquet canal and its anterior extension, the hyaloideocapsular ligament (also known as ligament of Weiger).
Excerpted from BCSC 2020-2021 series: Section 2 - Fundamentals and Principles of Ophthalmology. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.