Development of the Sensory Retina

Retinal Development

• At 4.5 months, retinal lamination is essentially complete, with layers including RPE, photoreceptors, outer plexiform layer, inner nuclear layer, inner plexiform layer, ganglion cell layer, and nerve fibres.
• At this stage, large cone nuclei are aligned adjacent to the RPE, and primitive lamellar synapses are established between bipolar cell dendrites and cone pedicles.

Formation of the Retina

• By 5.5 months, the retina has progressed, with growing photoreceptor outer segments projecting between RPE and external limiting membrane.
• The outer nuclear layer consists of 6-7 layers of nuclei, with cones aligned to the external limiting membrane.
• The outer plexiform layer has a linear arrangement of synapses between bipolar cells and rod spherules.

Foveal Development

• The fovea is the first part of the retina to develop but the last to mature, starting to form at approximately 22 weeks.
• The future fovea initially appears as a thickened layer of ganglion cell nuclei, which will later give way to the foveal pit.
• Cell migration plays a crucial role in foveal development, with ganglion and inner nuclear layer cells migrating away from the centre of the future fovea.
• Cones, particularly L- and M-cones, migrate into the fovea, increasing central cone density.

Retinal Cell Density

• Retinal cell density is determined by expansion, migration, and apoptosis.
• Foveal cell density is primarily a result of migration and lack of expansion.
• Peripheral cell density is due to a combination of migration away from the fovea, greater retinal expansion, and apoptosis of ganglion cells.

Formation of the Sensory Retina

• The retina has a centre-to-periphery developmental gradient, starting from the site of the future fovea and extending outward.
• Differentiation begins at about week 9 with the formation of ganglion cells, then horizontal cells and cones.
• By week 10, the first amacrine cells, rods, Müller's cells, and bipolar cells form.
• The same waves of cell development are apparent in the periphery, but begin later.
• The last rods, Müller's cells, and bipolar cells in the human retina are formed postnatally.

Synaptogenesis

• Synapse formation follows the same plan, occurring first in the fovea, about a week after the first cells in a given region are born, then spreading outward to the periphery.
• The formation of synapses between the major neuronal classes of the retina occurs in three major phases, starting with retinal ganglion cells and amacrine cells forming the earliest functional circuits of the inner plexiform layer.