Loss of CIB2 causes non-canonical autophagy deficits and visual impairment
Loss of CIB2 causes non-canonical autophagy deficits and visual impairment
SUMMARY Non-canonical autophagy or LC3-associated phagocytosis (LAP) is essential for the maintenance and functioning of the retinal pigment epithelium (RPE) and photoreceptors. Although molecular mechanisms still remain elusive, deficits in LAP have been found to be associated with age-related retinal pathology in both mice and humans. In this study, we found that calcium and integrin-binding protein 2 (CIB2) regulates LAP in the RPE. Mice lacking CIB2, both globally and specifically within RPE, have an impaired ability to process the engulfed photoreceptor outer segments due to reduced lysosomal capacity, which leads to marked accumulation of improperly digested remnants, lipid droplets, fused phago-melanosomes in RPE, and impaired visual function. In aged mice, we also found marked accumulation of drusen markers APOE, C3, and Aβ, along with esterified cholesterol. Intriguingly, we were able to transiently rescue the photoreceptor function in Cib2 mutant mice by exogenous retinoid delivery. Our study links LAP and phagocytic clearance with CIB2, and their relevance to the sense of sight.
Ahmed Zubair M.、Giese Arnaud P.J.、Scott Patrick A.、Duncan Todd、Redmond T. Michael、Riazuddin Saima、Sethna Saumil
Department of Otorhinolaryngology - Head & Neck Surgery, University of Maryland School of Medicine||Department of Ophthalmology and Visual Sciences, University of Maryland School of MedicineDepartment of Otorhinolaryngology - Head & Neck Surgery, University of Maryland School of MedicineDepartment of Ophthalmology & Visual Sciences, University of LouisvilleLaboratory of Retinal Cell and Molecular Biology, National Eye Institute, National Institutes of HealthLaboratory of Retinal Cell and Molecular Biology, National Eye Institute, National Institutes of HealthDepartment of Otorhinolaryngology - Head & Neck Surgery, University of Maryland School of MedicineDepartment of Otorhinolaryngology - Head & Neck Surgery, University of Maryland School of Medicine
眼科学基础医学分子生物学
CIB2phagocytosislysosomesphagolysosomesnon-canonical autophagyRPE9-cis retinalLC3-associated phagocytosis
Ahmed Zubair M.,Giese Arnaud P.J.,Scott Patrick A.,Duncan Todd,Redmond T. Michael,Riazuddin Saima,Sethna Saumil.Loss of CIB2 causes non-canonical autophagy deficits and visual impairment[EB/OL].(2025-03-28)[2025-05-10].https://www.biorxiv.org/content/10.1101/2020.09.18.302174.点此复制
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