{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T05:09:20Z","timestamp":1793423360703,"version":"4.5.0"},"reference-count":68,"publisher":"American Society for Clinical Investigation","issue":"10","license":[{"start":{"date-parts":[[2022,5,23]],"date-time":"2022-05-23T00:00:00Z","timestamp":1653264000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"crossref","award":["R01EY030991"],"award-info":[{"award-number":["R01EY030991"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"crossref"}]},{"name":"U.S. Department of Defense","award":["W81XWH-16-1-0699"],"award-info":[{"award-number":["W81XWH-16-1-0699"]}]},{"name":"National Science Foundation","award":["1904530"],"award-info":[{"award-number":["1904530"]}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"crossref","award":["P30EY08098"],"award-info":[{"award-number":["P30EY08098"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,5,23]]},"abstract":"<jats:p>\n                    <jats:italic>Rhodopsin<\/jats:italic>\n                    -associated (\n                    <jats:italic>RHO<\/jats:italic>\n                    -associated) retinitis pigmentosa (RP) is a progressive retinal disease that currently has no cure. RHO protein misfolding leads to disturbed proteostasis and the death of rod photoreceptors, resulting in decreased vision. We previously identified nonretinoid chaperones of RHO, including YC-001 and F5257-0462, by small-molecule high-throughput screening. Here, we profile the chaperone activities of these molecules toward the cell-surface level of 27 RP-causing human RHO mutants in NIH3T3 cells. Furthermore, using retinal explant culture, we show that YC-001 improves retinal proteostasis by supporting RHO homeostasis in\n                    <jats:italic>\n                      Rho\n                      <jats:sup>P23H\/+<\/jats:sup>\n                    <\/jats:italic>\n                    mouse retinae, which results in thicker outer nuclear layers (ONL), indicating delayed photoreceptor degeneration. Interestingly, YC-001 ameliorated retinal immune responses and reduced the number of microglia\/macrophages in the\n                    <jats:italic>\n                      Rho\n                      <jats:sup>P23H\/+<\/jats:sup>\n                    <\/jats:italic>\n                    retinal explants. Similarly, F5257-0462 also protects photoreceptors in\n                    <jats:italic>\n                      Rho\n                      <jats:sup>P23H\/+<\/jats:sup>\n                    <\/jats:italic>\n                    retinal explants. In vivo, intravitreal injection of YC-001 or F5257-0462 microparticles in PBS shows that F5257-0462 has a higher efficacy in preserving photoreceptor function and delaying photoreceptor death in\n                    <jats:italic>\n                      Rho\n                      <jats:sup>P23H\/+<\/jats:sup>\n                    <\/jats:italic>\n                    mice. Collectively, we provide proof of principle that nonretinoid chaperones are promising drug candidates in treating\n                    <jats:italic>RHO<\/jats:italic>\n                    -associated RP.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.153717","type":"journal-article","created":{"date-parts":[[2022,4,26]],"date-time":"2022-04-26T16:02:56Z","timestamp":1650988976000},"source":"Crossref","is-referenced-by-count":25,"title":["Nonretinoid chaperones improve rhodopsin homeostasis in a mouse model of retinitis pigmentosa"],"prefix":"10.1172","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4797-2136","authenticated-orcid":true,"given":"Abhishek","family":"Vats","sequence":"first","affiliation":[{"name":"Department of Ophthalmology,"},{"name":"Department of Pharmacology and Chemical Biology,"},{"name":"McGowan Institute of Regenerative Medicine, 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