Phagocytosis of Shed Photoreceptor Outer-Segment Discs
The RPE plays a crucial role in turnover of the photosensitive membrane of rod and cone photoreceptors (Fig 13-5). Each photoreceptor cell sheds approximately 100 outer-segment discs per day. Because many photoreceptors interdigitate with a single RPE cell, each RPE cell ingests and digests more than 4000 discs daily. The shedding event follows a circadian rhythm: in rods, shedding is most vigorous at dawn; in cones, shedding occurs most vigorously at dusk.
The shed outer-segment discs are encapsulated in phagosomes (see Fig 13-5C; see also Chapter 2, Fig 2-45), which in turn fuse with lysosomes and are digested. During degradation of the discs, building blocks are recycled into photoreceptors for use in the synthesis and assembly of new discs. The lipofuscin characteristic of the RPE is derived from the photosensitive membranes and is responsible for generating the signal detected in fundus autofluorescence imaging (Fig 13-6).
As detailed earlier in the chapter, phototransduction causes release of free all-trans-retinal, which is transported from the outer-segment discs into the outer-segment cytosol by ABCA4. In certain disease states (eg, Stargardt disease), the free all-trans-retinal is not readily cleared from the outer-segment discs by ABCA4. The excess all-trans-retinal combines with phosphatidylethanolamine (PE) in the disc lipid bilayer, forming N-retinylidene-PE (N-ret-PE). Elevated N-ret-PE and all-trans-retinal undergo a secondary nonenzymatic condensation in the outer segments to yield A2PE-H2. The distal outer segments containing A2PE-H2 and elevated all-trans-retinal and N-ret-PE are phagocytosed by the RPE as part of the normal disc-renewal process, but the RPE is unable to fully degrade the nonphysiologic load. This leads to the accumulation of toxic retinal fluorophores like A2E (derived from A2PE-H2), which damage the RPE.
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.