{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T18:00:01Z","timestamp":1781200801441,"version":"3.54.1"},"reference-count":43,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T00:00:00Z","timestamp":1781136000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 EY030056"],"award-info":[{"award-number":["R01 EY030056"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["EY031324"],"award-info":[{"award-number":["EY031324"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["EY032462"],"award-info":[{"award-number":["EY032462"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009455","name":"West Virginia University","doi-asserted-by":"publisher","award":["P20GM144230"],"award-info":[{"award-number":["P20GM144230"]}],"id":[{"id":"10.13039\/100009455","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001818","name":"Research to Prevent Blindness","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/100001818","id-type":"DOI","asserted-by":"publisher"}]},{"name":"BCM Families Foundation","award":["NA"],"award-info":[{"award-number":["NA"]}]},{"name":"West Virginia Lions and Lions Club International Foundation","award":["NA"],"award-info":[{"award-number":["NA"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Blue cone monochromacy (BCM) is an X-linked cone dystrophy characterized by loss of long- (L) and medium-wavelength (M) cone function. A common cause is the C203R missense mutation, which occurs in both\n                    <jats:italic>OPN1LW<\/jats:italic>\n                    and\n                    <jats:italic>OPN1MW<\/jats:italic>\n                    , or in hybrid\n                    <jats:italic>OPN1LW\/OPN1MW<\/jats:italic>\n                    opsin genes. Because BCM primarily affects foveal cones, we generated\n                    <jats:italic>Opn1mw<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>C198R<\/jats:italic>\n                    <\/jats:sup>\n                    <jats:italic>\/Opn1sw<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>-\/-<\/jats:italic>\n                    <\/jats:sup>\n                    <jats:italic>\/Nrl<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>-\/-<\/jats:italic>\n                    <\/jats:sup>\n                    (\n                    <jats:italic>C198RAC<\/jats:italic>\n                    ) mice carrying the murine equivalent of the human C203R mutation on an all-cone retinal background. C198RAC mice exhibited absent photopic ERG responses and significantly shortened cone outer segments, recapitulating foveal cone deficits in BCM. Metabolomic profiling further revealed altered retinal metabolism, including reduced cGMP and elevated oxidative stress\u2013related metabolites. To evaluate therapy, we delivered AAV8-Y733F expressing human L-opsin (OPN1LW) cDNA under the cone-specific PR2.1 promoter at 1 and 5 months of age. Treatment restored cone function, regenerated outer segment structures, and provided rescue for at least 5 months post-injection in both early- and late-treatment groups. These results demonstrate that densely packed cones expressing only the C198R mutant opsin remain viable targets for gene therapy. Together, this study establishes the\n                    <jats:italic>C198RAC<\/jats:italic>\n                    mouse as a cone-rich model mimicking foveal cone conditions in BCM and provides compelling preclinical evidence that AAV-mediated gene augmentation can rescue cone outer segment structure and function, supporting the feasibility of gene therapy for BCM.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0332684","type":"journal-article","created":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T17:24:08Z","timestamp":1781198648000},"page":"e0332684","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Gene therapy rescues cone function in an all-cone retina mouse model with the most common cone opsin C203R missense mutation"],"prefix":"10.1371","volume":"21","author":[{"given":"Marion E.","family":"Cahill","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2961-7525","authenticated-orcid":true,"given":"Kathryn","family":"Chmelik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5846-804X","authenticated-orcid":true,"given":"Brooke A.","family":"Brothers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madyson 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