Interphotoreceptor retinoid binding protein removes all-trans retinol and retinal from rod outer segments preventing lipofuscin precursor formation [Cell Biology]

Interphotoreceptor retinoid-binding protein (IRBP) is a specialized lipophilic carrier that binds the all-trans and 11-cis isomers of retinal and retinol, and facilitates their transport between photoreceptors and cells in the retina. One of these retinoids, all-trans retinal, is released in the rod outer segment by photoactivated rhodopsin after light excitation. Following its release, all-trans retinal is reduced by the retinol dehydrogenase RDH8 to all-trans retinol in an NADPH-dependent reaction. However, all-trans retinal can also react with outer segment components, sometimes forming lipofuscin precursors, which after conversion to lipofuscin accumulate in the lysosomes of the retinal pigment epithelium and display cytotoxic effects. Here, we have imaged the fluorescence of all-trans retinol, all-trans retinal, and lipofuscin precursors in real time in single isolated mouse rod photoreceptors. We found that IRBP removes all-trans retinol from individual rod photoreceptors in a concentration-dependent manner. The rate constant for retinol removal increased linearly with IRBP concentration with a slope of 0.012 min-1 μM-1. IRBP also removed all-trans retinal, but with much less efficacy, indicating that the reduction of retinal to retinol promotes faster clearance of the photoisomerized rhodopsin chromophore. The presence of physiological IRBP concentrations in the extracellular medium resulted in lower levels of all-trans retinal and retinol in rod outer segments following light exposure. It also prevented light-induced lipofuscin precursor formation, but did not remove precursors that were already present. These findings reveal an important and previously unappreciated role of IRBP in protecting the photoreceptor cells against the cytotoxic effects of accumulated all-trans retinal.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2fxDP2y
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