Retinal Pigment Epithelium

• Single layer of cuboidal epithelial cells
• Outermost retinal layer
• Between the choriocapillaris and the photoreceptor outer segments
• 4-6 million RPE cells per eye
• 45:1 photoreceptors:RPE

• Embryologically from the same tissue as the neural retina but differentiates into a secretory epithelium

• Cell bases face Bruchs, apices face neurosensory retina
• Long microvillous processes interdigitate with the photoreceptor outer segments

• Numerous melanin granules to absorb light
• RPE cells are more flattened in the periphery than in the centre

Biochemistry

• RPE contain enzymes for all 3 major energy producing pathways
• Glycolysis
• Kreb’s
• Pentose-phosphate pathway
• 80% water
• The Na/K ATPase is located on the apical surface (unique)
• Maintains the ionic balance in the subretinal space

• RNA is constantly synthesised for the production of enzymes for metabolism, phagocytosis of shed outer segment discs, maintenance of the retinoid cycle and transport

Function

• Metabolic
• Regeneration of visual pigment
• RPE stores high concentrations of vitamin A
• Recycles vitamin A after rhodopsin bleaching
• Uptake from the circulation
• From phagocytosed discs releasing vitamin A
• Generates 11-cis-retinaldehyde, which forms rhodopsin

• Converts retinol (product of the visual cycle) to a retinyl ester and then to 11-cis-retinol and finally back to 11-cis-retinal. This is returned to the photoreceptors by interphotoreceptor retinoid-binding protein (IRBP)

• Disposal/phagocytosis/detoxification of waste products and shed discs from the visual cycle

• Shed discs enter the cell in phagosome and fuse with lysosomes
• Disc components are recycled
• Each RPE disposes of more than 4000 discs per day
• Rod phagocytosis peaks just after light exposure
• Cone phagocytosis is more random and occurs at the onset of darkness
• Transports nutrients to the photoreceptors
• Physical/structural 
• Maintenance of adhesion between the retinal layers
• Hydrostatic forces
• Interdigitation of the outer segments by RPE microvilli
• Active transport of subretinal fluid/water via ocular dipole
• Maintenance/synthesis of the IPM
• Maintenance of the blood-retinal barrier
• Embryogenesis of photoreceptors
• Optical
• Absorption of scattered light
• Pigment granules are numerous within the RPE cytoplasm

• Triggering of melanogenesis is the key step in the embryological differentiation of the neuroectoderm into RPE

• There is age-related fusion of melanin granules with lysosomes so that older RPE is less pigmented

Melanin

• Derived from tyrosine (itself from phenylalanine)
• Rate determining step is the conversion of tyrosine to dopa by tyrosine hydroxylase
• Dopa is then converted by a non-enzymatic reaction
• Anti-oxidant properties and contains stable free radicals
• Effective free radical scavenger in the RPE which it protects 
• Melanin is lost with age: may contribute to ARMD

RPE pathology

• Sorsby fundus dystrophy
• Autosomal recessive retinitis pigmentosa
• Vitelliform macular degeneration (Best disease)
• Malattia leventinese (dominant drusen)
• ARMD
• Stargardt disease