Dominant role for pigment epithelial CRALBP in supplying visual chromophore to photoreceptors
Marco Bassetto,
Alexander V. Kolesnikov,
Dominik Lewandowski,
Jianying Z. Kiser,
Maximilian Halabi,
David E. Einstein,
Elliot H. Choi,
Krzysztof Palczewski,
Vladimir J. Kefalov,
Philip D. Kiser
Affiliations
Marco Bassetto
Department 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
Alexander V. Kolesnikov
Center for Translational Vision Research, Gavin Herbert Eye Institute, Department of Ophthalmology, University of California Irvine, Irvine, CA 92697, USA
Dominik Lewandowski
Center for Translational Vision Research, Gavin Herbert Eye Institute, Department of Ophthalmology, University of California Irvine, Irvine, CA 92697, USA
Jianying Z. Kiser
Department of Physiology & Biophysics, University of California Irvine, Irvine, CA 92697, USA; Center for Translational Vision Research, Gavin Herbert Eye Institute, Department of Ophthalmology, University of California Irvine, Irvine, CA 92697, USA
Maximilian Halabi
Department of Physiology & Biophysics, University of California Irvine, Irvine, CA 92697, USA
David E. Einstein
Department 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
Elliot H. Choi
Center for Translational Vision Research, Gavin Herbert Eye Institute, Department of Ophthalmology, University of California Irvine, Irvine, CA 92697, USA
Krzysztof Palczewski
Department of Physiology & Biophysics, University of California Irvine, Irvine, CA 92697, USA; Center for Translational Vision Research, Gavin Herbert Eye Institute, Department of Ophthalmology, University of California Irvine, Irvine, CA 92697, USA; Department of Chemistry, University of California Irvine, Irvine, CA 92697, USA; Department of Molecular Biology and Biochemistry, University of California Irvine, Irvine, CA 92697, USA
Vladimir J. Kefalov
Department of Physiology & Biophysics, University of California Irvine, Irvine, CA 92697, USA; Center for Translational Vision Research, Gavin Herbert Eye Institute, Department of Ophthalmology, University of California Irvine, Irvine, CA 92697, USA
Philip D. Kiser
Department 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; Department of Clinical Pharmacy Practice, University of California Irvine, Irvine, CA 92697, USA; Corresponding author
Summary: 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.
