{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T22:00:16Z","timestamp":1791928816573,"version":"4.3.4"},"reference-count":53,"publisher":"Association for Research in Vision and Ophthalmology (ARVO)","issue":"13","license":[{"start":{"date-parts":[[2023,10,26]],"date-time":"2023-10-26T00:00:00Z","timestamp":1698278400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Invest. Ophthalmol. Vis. Sci."],"published-print":{"date-parts":[[2023,10,26]]},"DOI":"10.1167\/iovs.64.13.41","type":"journal-article","created":{"date-parts":[[2023,10,26]],"date-time":"2023-10-26T11:30:50Z","timestamp":1698319850000},"page":"41","source":"Crossref","is-referenced-by-count":6,"title":["Proteopathy Linked to Exon-Skipping Isoform of RGR-Opsin Contributes to the Pathogenesis of Age-Related Macular Degeneration"],"prefix":"10.1167","volume":"64","author":[{"given":"Chi","family":"Ren","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Eye Disease and Optometry Institute, Peking University People's Hospital, Beijing, China"},{"name":"Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoran","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Eye Disease and Optometry Institute, Peking University People's Hospital, Beijing, China"},{"name":"Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, Beijing, China"},{"name":"Department of Ophthalmology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Bao","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Eye Disease and Optometry Institute, Peking University People's Hospital, Beijing, China"},{"name":"Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, Beijing, China"},{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lvzhen","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Eye Disease and Optometry Institute, Peking University People's Hospital, Beijing, China"},{"name":"Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shikun","family":"He","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, USC Roski Eye Institute, Keck School of Medicine of University of Southern California, Los Angeles, California, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry K. W.","family":"Fong","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, USC Roski Eye Institute, Keck School of Medicine of University of Southern California, Los Angeles, California, United States"},{"name":"Department of Molecular Microbiology and Immunology, University of Southern California, Los Angeles, California, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingwei","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Eye Disease and Optometry Institute, Peking University People's Hospital, Beijing, China"},{"name":"Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"27","reference":[{"issue":"18","key":"bib1","doi-asserted-by":"publisher","first-page":"6647","DOI":"10.3390\/ijms21186647","article-title":"An in-vitro cell model of intracellular protein aggregation provides insights into RPE stress associated with retinopathy","volume":"21","author":"Keeling","year":"2020","journal-title":"Int J Mol Sci"},{"issue":"8","key":"bib2","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1038\/nrneurol.2017.99","article-title":"ER stress and the unfolded protein response in neurodegeneration","volume":"13","author":"Hetz","year":"2017","journal-title":"Nat Rev Neurol"},{"issue":"6","key":"bib3","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1016\/j.neuron.2023.01.016","article-title":"Neurodegeneration cell per cell","volume":"111","author":"Balusu","year":"2023","journal-title":"Neuron"},{"key":"bib4","first-page":"27","article-title":"Histopathology of age-related macular degeneration","volume":"5","author":"Green","year":"1999","journal-title":"Mol Vis"},{"issue":"1","key":"bib5","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1038\/eye.2016.216","article-title":"Structural and molecular changes in the aging choroid: implications for age-related macular degeneration","volume":"31","author":"Chirco","year":"2017","journal-title":"Eye (Lond)"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.preteyeres.2015.09.002","article-title":"Defects in retinal pigment epithelial cell proteolysis and the pathology associated with age-related macular degeneration","volume":"51","author":"Ferrington","year":"2016","journal-title":"Prog Retin Eye Res"},{"issue":"11","key":"bib7","doi-asserted-by":"publisher","first-page":"e13257","DOI":"10.1111\/acel.v19.11","article-title":"Autophagic receptor p62 protects against glycation-derived toxicity and enhances viability","volume":"19","author":"Aragon\u00e8s","year":"2020","journal-title":"Aging Cell"},{"issue":"1","key":"bib8","doi-asserted-by":"publisher","first-page":"210","DOI":"10.3390\/ijms20010210","article-title":"Interplay between autophagy and the ubiquitin-proteasome system and its role in the pathogenesis of age-related macular degeneration","volume":"20","author":"Blasiak","year":"2019","journal-title":"Int J Mol Sci"},{"issue":"10","key":"bib9","doi-asserted-by":"publisher","first-page":"2656","DOI":"10.1172\/JCI26373","article-title":"Endoplasmic reticulum stress: cell life and death decisions","volume":"115","author":"Xu","year":"2005","journal-title":"J Clin Invest"},{"issue":"6968","key":"bib10","doi-asserted-by":"publisher","first-page":"891","DOI":"10.1038\/nature02262","article-title":"Quality control in the endoplasmic reticulum protein factory","volume":"426","author":"Sitia","year":"2003","journal-title":"Nature"},{"issue":"6467","key":"bib11","doi-asserted-by":"publisher","first-page":"818","DOI":"10.1126\/science.aax3769","article-title":"Cellular quality control by the ubiquitin-proteasome system and autophagy","volume":"366","author":"Pohl","year":"2019","journal-title":"Science"},{"issue":"13","key":"bib12","doi-asserted-by":"publisher","first-page":"e12165","DOI":"10.1002\/jev2.v10.13","article-title":"Extracellular vesicles released by human retinal pigment epithelium mediate increased polarised secretion of drusen proteins in response to AMD stressors","volume":"10","author":"Flores-Bellver","year":"2021","journal-title":"J Extracell Vesicles"},{"issue":"45","key":"bib13","doi-asserted-by":"publisher","first-page":"18277","DOI":"10.1073\/pnas.1109703108","article-title":"Cell culture model that mimics drusen formation and triggers complement activation associated with age-related macular degeneration","volume":"108","author":"Johnson","year":"2011","journal-title":"Proc Natl Acad Sci USA"},{"issue":"39","key":"bib14","doi-asserted-by":"publisher","first-page":"E8214","DOI":"10.1073\/pnas.1710430114","article-title":"Drusen in patient-derived hiPSC-RPE models of macular dystrophies","volume":"114","author":"Galloway","year":"2017","journal-title":"Proc Natl Acad Sci USA"},{"issue":"4","key":"bib15","doi-asserted-by":"crossref","first-page":"jcs215798","DOI":"10.1242\/jcs.215798","article-title":"In vitro drusen model\u2014three-dimensional spheroid culture of retinal pigment epithelial cells","volume":"132","author":"Usui","year":"2018","journal-title":"J Cell Sci"},{"issue":"13","key":"bib16","first-page":"3669","article-title":"An opsin homologue in the retina and pigment epithelium","volume":"34","author":"Jiang","year":"1993","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"4","key":"bib17","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1016\/S0014-4835(05)80096-X","article-title":"Alternative splicing in human retinal mRNA transcripts of an opsin-related protein","volume":"60","author":"Jiang","year":"1995","journal-title":"Exp Eye Res"},{"issue":"1","key":"bib18","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/j.exer.2005.11.013","article-title":"Exon-skipping variant of RGR opsin in human retina and pigment epithelium","volume":"83","author":"Fong","year":"2006","journal-title":"Exp Eye Res"},{"issue":"6","key":"bib19","doi-asserted-by":"publisher","first-page":"1172","DOI":"10.1016\/j.neuron.2019.04.004","article-title":"Light-driven regeneration of cone visual pigments through a mechanism involving RGR opsin in M\u00fcller glial cells","volume":"102","author":"Morshedian","year":"2019","journal-title":"Neuron"},{"key":"bib20","doi-asserted-by":"publisher","first-page":"100040","DOI":"10.1194\/jlr.TR120000850","article-title":"Retinoids in the visual cycle: role of the retinal G protein-coupled receptor","volume":"62","author":"Choi","year":"2021","journal-title":"J Lipid Res"},{"key":"bib21","doi-asserted-by":"publisher","first-page":"100072","DOI":"10.1074\/jbc.REV120.014405","article-title":"Pathways and disease-causing alterations in visual chromophore production for vertebrate vision","volume":"296","author":"Kiser","year":"2021","journal-title":"J Biol Chem"},{"issue":"8","key":"bib22","doi-asserted-by":"publisher","first-page":"1454","DOI":"10.1016\/j.ajpath.2021.05.003","article-title":"Human RGR gene and associated features of age-related macular degeneration in models of retina-choriocapillaris atrophy","volume":"191","author":"Bao","year":"2021","journal-title":"Am J Pathol"},{"key":"bib23","first-page":"1203","article-title":"Deposition of exon-skipping splice isoform of human retinal G protein-coupled receptor from retinal pigment epithelium into Bruch's membrane","volume":"13","author":"Lin","year":"2007","journal-title":"Mol Vis"},{"issue":"16","key":"bib24","doi-asserted-by":"publisher","first-page":"9420","DOI":"10.1111\/jcmm.v24.16","article-title":"MeCP2-421-mediated RPE epithelial-mesenchymal transition and its relevance to the pathogenesis of proliferative vitreoretinopathy","volume":"24","author":"Li","year":"2020","journal-title":"J Cell Mol Med"},{"issue":"2","key":"bib25","first-page":"189","article-title":"Efficacy of tribromoethanol anesthesia in mice","volume":"43","author":"Papaioannou","year":"1993","journal-title":"Lab Anim Sci"},{"issue":"8","key":"bib26","doi-asserted-by":"publisher","first-page":"1437","DOI":"10.1080\/15548627.2015.1066957","article-title":"Bafilomycin A1 disrupts autophagic flux by inhibiting both V-ATPase-dependent acidification and Ca-P60A\/SERCA-dependent autophagosome-lysosome fusion","volume":"11","author":"Mauvezin","year":"2015","journal-title":"Autophagy"},{"key":"bib27","first-page":"213","article-title":"Targeting of exon VI-skipping human RGR-opsin to the plasma membrane of pigment epithelium and co-localization with terminal complement complex C5b-9","volume":"22","author":"Kochounian","year":"2016","journal-title":"Mol Vis"},{"issue":"8","key":"bib28","doi-asserted-by":"publisher","first-page":"1170","DOI":"10.3390\/antiox10081170","article-title":"Mitochondrial dysfunction and endoplasmic reticulum stress in age related macular degeneration, role in pathophysiology, and possible new therapeutic strategies","volume":"10","author":"Bilbao-Malav\u00e9","year":"2021","journal-title":"Antioxidants (Basel)"},{"issue":"1","key":"bib29","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1186\/s13024-022-00528-w","article-title":"Cellular stress signaling and the unfolded protein response in retinal degeneration: mechanisms and therapeutic implications","volume":"17","author":"McLaughlin","year":"2022","journal-title":"Mol Neurodegener"},{"issue":"8","key":"bib30","doi-asserted-by":"publisher","first-page":"696","DOI":"10.1016\/j.tcb.2022.02.005","article-title":"Quality control of protein complex assembly by the ubiquitin-proteasome system","volume":"32","author":"Pla-Prats","year":"2022","journal-title":"Trends Cell Biol"},{"issue":"3","key":"bib31","doi-asserted-by":"publisher","first-page":"a023523","DOI":"10.1101\/cshperspect.a023523","article-title":"Protein quality control in health and disease","volume":"9","author":"Dubnikov","year":"2017","journal-title":"Cold Spring Harb Perspect Biol"},{"issue":"1","key":"bib32","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1016\/j.bbamcr.2013.06.031","article-title":"Protein quality control and elimination of protein waste: the role of the ubiquitin-proteasome system","volume":"1843","author":"Amm","year":"2014","journal-title":"Biochim Biophys Acta"},{"issue":"1","key":"bib33","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1002\/art.v66.1","article-title":"Dual role of autophagy in stress-induced cell death in rheumatoid arthritis synovial fibroblasts","volume":"66","author":"Kato","year":"2014","journal-title":"Arthritis Rheumatol"},{"key":"bib34","doi-asserted-by":"publisher","first-page":"101032","DOI":"10.1016\/j.preteyeres.2021.101032","article-title":"Clusterin, other extracellular chaperones, and eye disease","volume":"89","author":"Wilson","year":"2022","journal-title":"Prog Retin Eye Res"},{"issue":"9","key":"bib35","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1002\/prot.v87.9","article-title":"Effect of site-directed point mutations on protein misfolding: a simulation study","volume":"87","author":"Kumar","year":"2019","journal-title":"Proteins"},{"issue":"1","key":"bib36","doi-asserted-by":"publisher","first-page":"e0210361","DOI":"10.1371\/journal.pone.0210361","article-title":"Experimental approach to study the effect of mutations on the protein folding pathway","volume":"14","author":"Nemtseva","year":"2019","journal-title":"PLoS One"},{"issue":"7","key":"bib37","doi-asserted-by":"publisher","first-page":"1413","DOI":"10.1002\/jcp.24923","article-title":"Role of the unfolded protein response, GRP78 and GRP94 in organ homeostasis","volume":"230","author":"Zhu","year":"2015","journal-title":"J Cell Physiol"},{"key":"bib38","doi-asserted-by":"publisher","first-page":"118317","DOI":"10.1016\/j.lfs.2020.118317","article-title":"GRP78 targeting: hitting two birds with a stone","volume":"260","author":"Elfiky","year":"2020","journal-title":"Life Sci"},{"issue":"11","key":"bib39","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1038\/nrneph.2017.129","article-title":"Endoplasmic reticulum stress, the unfolded protein response and autophagy in kidney diseases","volume":"13","author":"Cybulsky","year":"2017","journal-title":"Nat Rev Nephrol"},{"issue":"2","key":"bib40","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1038\/nrm3270","article-title":"The unfolded protein response: controlling cell fate decisions under ER stress and beyond","volume":"13","author":"Hetz","year":"2012","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"3","key":"bib41","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1038\/ncb0311-184","article-title":"Integrating the mechanisms of apoptosis induced by endoplasmic reticulum stress","volume":"13","author":"Tabas","year":"2011","journal-title":"Nat Cell Biol"},{"issue":"9","key":"bib42","doi-asserted-by":"publisher","first-page":"1765","DOI":"10.1007\/s00018-016-2147-8","article-title":"Inflammation and its role in age-related macular degeneration","volume":"73","author":"Kauppinen","year":"2016","journal-title":"Cell Mol Life Sci"},{"key":"bib43","doi-asserted-by":"publisher","first-page":"101248","DOI":"10.1016\/j.eclinm.2021.101248","article-title":"Patients with MPNs and retinal drusen show signs of complement system dysregulation and a high degree of chronic low-grade inflammation","volume":"43","author":"Liisborg","year":"2022","journal-title":"EClinicalMedicine"},{"key":"bib44","doi-asserted-by":"publisher","first-page":"108440","DOI":"10.1016\/j.exer.2021.108440","article-title":"Impacts of high fat diet on ocular outcomes in rodent models of visual disease","volume":"204","author":"Clarkson-Townsend","year":"2021","journal-title":"Exp Eye Res"},{"issue":"11","key":"bib45","doi-asserted-by":"publisher","first-page":"e2100823","DOI":"10.1002\/mnfr.v66.11","article-title":"A high fat \u201cWestern-style\u201d diet induces AMD-like features in wildtype mice","volume":"66","author":"Keeling","year":"2022","journal-title":"Mol Nutr Food Res"},{"issue":"23","key":"bib46","doi-asserted-by":"publisher","first-page":"E3040","DOI":"10.1073\/pnas.1424391112","article-title":"Regulation of age-related macular degeneration-like pathology by complement factor H","volume":"112","author":"Toomey","year":"2015","journal-title":"Proc Natl Acad Sci USA"},{"issue":"11","key":"bib47","doi-asserted-by":"publisher","first-page":"2579","DOI":"10.3390\/nu11112579","article-title":"Effect of high-fat diets on oxidative stress, cellular inflammatory response and cognitive function","volume":"11","author":"Tan","year":"2019","journal-title":"Nutrients"},{"key":"bib48","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1016\/j.bbi.2019.02.016","article-title":"Short-term high-fat diet modulates several inflammatory, ER stress, and apoptosis markers in the hippocampus of young mice","volume":"79","author":"Nakandakari","year":"2019","journal-title":"Brain Behav Immun"},{"key":"bib49","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1016\/j.freeradbiomed.2021.10.022","article-title":"High-fat diet aggravates colitis-associated carcinogenesis by evading ferroptosis in the ER stress-mediated pathway","volume":"177","author":"Zhang","year":"2021","journal-title":"Free Radic Biol Med"},{"issue":"5","key":"bib50","doi-asserted-by":"publisher","first-page":"794","DOI":"10.1016\/j.immuni.2019.09.020","article-title":"Western diet and the immune system: an inflammatory connection","volume":"51","author":"Christ","year":"2019","journal-title":"Immunity"},{"issue":"1","key":"bib51","doi-asserted-by":"publisher","first-page":"1322","DOI":"10.1038\/s41467-021-21715-1","article-title":"VPS34 K29\/K48 branched ubiquitination governed by UBE3C and TRABID regulates autophagy, proteostasis and liver metabolism","volume":"12","author":"Chen","year":"2021","journal-title":"Nat Commun"},{"issue":"8","key":"bib52","doi-asserted-by":"publisher","first-page":"112982","DOI":"10.1016\/j.celrep.2023.112982","article-title":"Rapid RGR-dependent visual pigment recycling is mediated by the RPE and specialized M\u00fcller glia","volume":"42","author":"Tworak","year":"2023","journal-title":"Cell Rep"},{"key":"bib53","doi-asserted-by":"publisher","first-page":"982073","DOI":"10.3389\/fevo.2022.982073","article-title":"Molecular evolution of vision-related genes may contribute to marsupial photic niche adaptations","volume":"10","author":"Tian","year":"2022","journal-title":"Front Ecol Evol"}],"container-title":["Investigative Opthalmology &amp; Visual Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/iovs.arvojournals.org\/article.aspx?articleid=2792959","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:31:44Z","timestamp":1791927104000},"score":1,"resource":{"primary":{"URL":"https:\/\/iovs.arvojournals.org\/article.aspx?articleid=2792959"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,26]]},"references-count":53,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2023,10,3]]}},"URL":"https:\/\/doi.org\/10.1167\/iovs.64.13.41","relation":{},"ISSN":["1552-5783"],"issn-type":[{"value":"1552-5783","type":"print"}],"subject":[],"published":{"date-parts":[[2023,10,26]]}}}