Retinal pigment epithelium

Stratum pigmentosum retinae

Also known as: RPE, pigment epithelium

A single layer of hexagonal pigmented cells between the photoreceptors and Bruch membrane that sustains photoreceptor function: it recycles visual pigment, phagocytoses shed outer segments, absorbs stray light and forms the outer blood–retina barrier.

Overview

The RPE derives from the outer layer of the optic cup. Each cell (≈3.5–5 million in total) faces ≈30–45 photoreceptor outer segments with long apical microvilli that interdigitate with them; its basal surface is infolded on Bruch membrane. Neighbouring cells are joined by tight junctions, forming the outer blood–retina barrier that isolates the neural retina from the leaky (fenestrated) choriocapillaris.

Its functions are indispensable: (1) visual cycle — all-trans-retinol released from bleached rhodopsin is taken up, esterified and isomerised by the enzyme RPE65 to 11-cis-retinal, which is returned to the photoreceptors; (2) phagocytosis — every day photoreceptors shed ≈10% of their outer-segment discs (rods mainly at dawn, cones at dusk), which the RPE engulfs and digests — each RPE cell is among the most phagocytically active cells in the body; (3) light absorption by melanin, reducing scatter, and antioxidant protection; (4) transport of nutrients, ions and water (pumping fluid out of the subretinal space helps keep the retina attached); (5) secretion of growth factors (e.g. PEDF, VEGF towards the choriocapillaris).

Incomplete digestion of outer segments leaves lipofuscin (A2E), which accumulates with age and contributes to age-related macular degeneration.

Location

Outermost layer of the retina, between the photoreceptor outer segments and Bruch membrane/choroid.

Function

Regenerate 11-cis-retinal (visual cycle)

Phagocytose and digest shed photoreceptor outer-segment discs

Absorb stray light (melanin) and neutralise free radicals

Form the outer blood–retina barrier and transport nutrients, ions and water

Maintain adhesion of the neural retina (subretinal fluid pumping)

Clinical significance

Leber congenital amaurosis and gene therapy

Biallelic RPE65 mutations prevent regeneration of 11-cis-retinal, causing severe early-onset blindness. Voretigene neparvovec (subretinal AAV gene therapy) was the first approved gene therapy for an inherited disease.

Drusen and AMD

Extracellular deposits (drusen) between RPE and Bruch membrane, RPE atrophy (geographic atrophy) and breaches of Bruch membrane by choroidal vessels are the lesions of age-related macular degeneration.

Drug toxicity

Hydroxychloroquine accumulates in the RPE (melanin-binding) and can cause bull's-eye maculopathy; regular screening is required on long-term therapy.