ArticleAutophagy2014
Lysosomal-mediated waste clearance in retinal pigment epithelial cells is regulated by CRYBA1/βA3/A1-crystallin via V-ATPase-MTORC1 signaling.
Article in Autophagy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers.
What it found
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Who cites it
104 citing papers in PubMed, 139 citations in OpenAlex.
- Sustained proton-pump inhibitor exposure and incident age-related macular degeneration: a new-user, population-based cohort study.BMJ open ophthalmology · 2026Observational
- Caveola and Its Resident Proteins, Caveolin-1 and -2, Play Critical Roles in the Pathogenesis of nAMD and PCV.Investigative ophthalmology & visual science · 2026Article
- ATP6V0A1 protects dopaminergic neurons via the autophagy-lysosomal pathway in Parkinson's disease.Neural regeneration research · 2026Article
- PIKfyve preserves endolysosomal function in photoreceptors and RPE cells to maintain retinal integrity.Cell death & disease · 2026Article
- NAMPT Deficiency Promotes Endothelial-Mesenchymal Transition by Inhibiting Energy Metabolism and Lysosomal Acidification in Late-Onset Fuchs Endothelial Corneal Dystrophy.Investigative ophthalmology & visual science · 2026Article
- STING activation induces polarized cytokine secretion of IFN-β and IL-17A promoting photoreceptor death and choroidal disruption in age-related macular degeneration.Cell death & disease · 2026Article
- PLGA nanoparticles restore acidic pH and degradative function to compromised lysosomes with Cy3-labeling providing enhanced tracking to lysosomes.American journal of physiology. Cell physiology · 2026Article
- AI driven 3D subcellular RPE map discovers cell state transitions in establishment of apical-basal polarity.NPJ artificial intelligence · 2026Article
- Article
- Sustained Lysosomal Delivery of Enhanced Cy3-Labeled Acid Nanoparticles Restores Lysosomal pH in Retinal Pigment Epithelial Cells and Astrocytes.bioRxiv : the preprint server for biology · 2025Article
- Activated mTOR Signaling in the RPE Drives EMT, Autophagy, and Metabolic Disruption, Resulting in AMD-Like Pathology in Mice.Aging cell · 2025Article
- Single-cell RNA sequencing highlights a significant retinal Müller glial population in dry age-related macular degeneration.iScience · 2025Article
- Beacon of Hope for Age-Related Retinopathy: Antioxidative Mechanisms and Pre-Clinical Trials of Quercetin Therapy.Antioxidants (Basel, Switzerland) · 2025Review
- How crosstalk between mitochondria, lysosomes, and other organelles can prevent or promote dry age-related macular degeneration.Experimental eye research · 2025Review
- Retinal Pigment Epithelium Under Oxidative Stress: Chaperoning Autophagy and Beyond.International journal of molecular sciences · 2025Review
- G91-deletion in βA3/A1-crystallin induces cellular and molecular changes in mouse lenses leading to congenital cataract development.PloS one · 2025Article
- Aging of the eye: Lessons from cataracts and age-related macular degeneration.Ageing research reviews · 2024Review
- The AKT2/SIRT5/TFEB pathway as a potential therapeutic target in non-neovascular AMD.Nature communications · 2024Article
- Neutrophils in Ocular Diseases.International journal of molecular sciences · 2024Review
- Dysregulation of Autophagy Occurs During Congenital Cataract Development in βA3ΔG91 Mice.Investigative ophthalmology & visual science · 2024Article
44 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
20 authors at 6 institutions in 2 countries.
Funding
Abstract
In phagocytic cells, including the retinal pigment epithelium (RPE), acidic compartments of the endolysosomal system are regulators of both phagocytosis and autophagy, thereby helping to maintain cellular homeostasis. The acidification of the endolysosomal system is modulated by a proton pump, the V-ATPase, but the mechanisms that direct the activity of the V-ATPase remain elusive. We found that in RPE cells, CRYBA1/βA3/A1-crystallin, a lens protein also expressed in RPE, is localized to lysosomes, where it regulates endolysosomal acidification by modulating the V-ATPase, thereby controlling both phagocytosis and autophagy. We demonstrated that CRYBA1 coimmunoprecipitates with the ATP6V0A1/V0-ATPase a1 subunit. Interestingly, in mice when Cryba1 (the gene encoding both the βA3- and βA1-crystallin forms) is knocked out specifically in RPE, V-ATPase activity is decreased and lysosomal pH is elevated, while cathepsin D (CTSD) activity is decreased. Fundus photographs of these Cryba1 conditional knockout (cKO) mice showed scattered lesions by 4 months of age that increased in older mice, with accumulation of lipid-droplets as determined by immunohistochemistry. Transmission electron microscopy (TEM) of cryba1 cKO mice revealed vacuole-like structures with partially degraded cellular organelles, undigested photoreceptor outer segments and accumulation of autophagosomes. Further, following autophagy induction both in vivo and in vitro, phospho-AKT and phospho-RPTOR/Raptor decrease, while pMTOR increases in RPE cells, inhibiting autophagy and AKT-MTORC1 signaling. Impaired lysosomal clearance in the RPE of the cryba1 cKO mice also resulted in abnormalities in retinal function that increased with age, as demonstrated by electroretinography. Our findings suggest that loss of CRYBA1 causes lysosomal dysregulation leading to the impairment of both autophagy and phagocytosis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.