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Published on: December 27, 2024
Dominant role for pigment epithelial CRALBP in supplying visual chromophore to photoreceptors
Marco Bassetto1, Alexander V Kolesnikov2, Dominik Lewandowski2
1Department of Physiology & Biophysics, University of California Irvine, Irvine, CA 92697, USA; Research Service, Tibor Rubin VA Long Beach Medical Center, Long Beach, CA 90822, USA; Center for Translational Vision Research, Gavin Herbert Eye Institute, Department of Ophthalmology, University of California Irvine, Irvine, CA 92697, USA.
Abstract:
Cellular retinaldehyde-binding protein (CRALBP) supports production of 11-cis-retinaldehyde and its delivery to photoreceptors. It is found in the retinal pigment epithelium (RPE) and Müller glia (MG), but the relative functional importance of these two cellular pools is debated. Here, we report RPE- and MG-specific CRALBP knockout (KO) mice and examine their photoreceptor and visual cycle function. Bulk visual chromophore regeneration in RPE-KO mice is 15-fold slower than in controls, accounting for their delayed rod dark adaptation and protection against retinal phototoxicity, whereas MG-KO mice have normal bulk visual chromophore regeneration and retinal light damage susceptibility. Cone pigment regeneration is significantly impaired in RPE-KO mice but mildly affected in MG-KO mice, disclosing an unexpectedly strong reliance of cone photoreceptors on the RPE-based visual cycle. These data reveal a dominant role for RPE-CRALBP in supporting rod and cone function and highlight the importance of RPE cell targeting for CRALBP gene therapies.
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