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Silvia C. Finnemann, Linda Ruggiero, Mark P. Connor; Diurnal Photoreceptor Outer Segment Shedding: Contributions Of The RPE. Invest. Ophthalmol. Vis. Sci. 2012;53(14):4327.
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In the mammalian retina, life-long renewal of light-sensitive photoreceptor outer segments (POS) involves circadian shedding of distal rod POS tips and their subsequent phagocytosis by the adjacent retinal pigment epithelium (RPE) every morning after light onset. We set out to identify molecular mechanisms that promote or synchronize POS tip shedding, which have thus far been unknown.
We examined plasma membrane asymmetry of live POS by quantifying surface exposure of the membrane phospholipid phosphatidylserine (PS) using antibodies, annexinV, and pSIVA, an annexin-based biosensor with switchable states of fluorescence.
We found that isolated phagocytic POS particles possess externalized PS whose blockade reduces their uptake by RPE in culture. Live imaging of photoreceptors in mouse retina detected PS externalization that is restricted to POS tips with discrete boundaries. In wild-type mice, frequency of rod tips exposing PS and length of tips with exposed PS peak shortly after light onset. In contrast, PS-marked POS tips do not vary in mice lacking the diurnal phagocytic rhythm of the RPE due to loss of either the phagocytosis receptor αvβ5 integrin, expressed by the RPE but not by photoreceptors, or its extracellular ligand MFG-E8.
Enhanced PS exposure preceding rod shedding and phagocytosis suggests that surface PS promotes these processes. Moreover, our results demonstrate that the diurnal rhythm of PS-demarcation of POS tips is not intrinsic to rod photoreceptors but requires activities of the RPE as well.
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