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The Retina (6) Retinal Pigment Epithelium (RPE) SFO1002 Dr R S Mughal Learning Outcome s • Describe the functions of RPE • Describe the process of photopigment regeneration • Describe the process of shedding and renewal of photoreceptors Functions of the RPE • Absorption of scattered light • Ph...

The Retina (6) Retinal Pigment Epithelium (RPE) SFO1002 Dr R S Mughal Learning Outcome s • Describe the functions of RPE • Describe the process of photopigment regeneration • Describe the process of shedding and renewal of photoreceptors Functions of the RPE • Absorption of scattered light • Physical support for photoreceptors • Trafficking of nutrients from choroid to outer retina • Renewal of photoreceptor discs • Regeneration of photopigment Properties of the RPE • Outermost retinal layer • Single cell thick • Pigmented cells • Contain melanosomes • Basal aspect • Strong attachment to choroid • Contains numerous infoldings • Apical aspect • Faces neural retina • Contains microvilli that extend up to the outer segment of photoreceptors • Tight junctions near the apical surface form the blood-retinal barrier Properties of the RPE • RPE processes and photoreceptors are not directly attached to each other • Interphotoreceptor matrix (IPM) • The material that occupies this small space • IPM keeps the RPE and photoreceptors attached to each other • IPM made from a mixture of proteins and glycosaminoglycans • IMP provides a means for exchange of metabolites between the two cells. RPE and photoreceptor interface: A common location for a retinal detachment • The interface between the RPE and photoreceptors doesn’t contain any cellular junctions • Although IPM adheres both cells together, a separation at this interface is a common location in retinal detachment Shedding and renewal of photoreceptor discs • Photoreceptors under constant oxidative stress (UV radiation) • Cycle of shedding and renewal • Photoreceptor discs are shed and renewed every day • Continuous removal of old discs and replacement with new ones. Shedding and renewal of photoreceptor discs • New discs are made in the inner segment and transported to the base of outer segment • Old discs are removed from the tip of the outer segment • Removal of old discs is called shedding • RPE phagocytose old discs Shedding through phagocytosis • RPE contain numerous lysosomes allowing it to phagocytose old discs • Enable RPE to ingest up to 2000 discs per day. • Shedding regulated by the circadian rhythm Regeneration of bleached photopigment Regeneration of bleached photopigmen t • To replenish photopigment, transretinal is recycled back into 11cis-retinal • This process occurs in the RPE • RPE stores vitamin A (11-cis-retinal is a derivative of vitA) • Involves a series of enzymatic steps • May be multiple pathways involved • We will focus on one of the most well known Regeneration of bleached photopigment • Trans-retinal is shuttled across the IPM to the RPE for recycling • Retinals require a carrier protein when outside of the photoreceptor • Interstitial retinoid binding protein (IRBP) is the carrier protein which exists in the IPM • IRBP chaperones transretinal from the photoreceptor to the RPE. Regeneration of bleached photopigment • In the RPE, trans retinal binds to another carrier protein. • Here, it undergoes a number of enzymatic reactions to be transformed back into 11-cisretinal. • RPE65 is one of the main proteins involved in the conversion of trans- to 11-cis-retinal. • 11-cis-retinal shuttled back to the photoreceptor via IRBP • In the photoreceptor, 11-cis-retinal binds to Opsin to form photopigment. Regeneration of bleached photopigment Summary • RPE is essential for the health of photoreceptors • Exchange of nutrients • Shedding and renewal of photoreceptor discs • Regeneration of photopigment • If photoreceptors are separated from the RPE, this will affect photoreceptor health Supplementary Reading • Remington • Page 61 (Retinal pigment epithelium) • Page 62 (Retinal Pigment Epithelium-Neuroretinal Interface) • Page 75-76 (Physiology of the RPE)

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