{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T21:17:28Z","timestamp":1777670248393,"version":"3.51.4"},"reference-count":44,"publisher":"SAGE Publications","issue":"13-14","license":[{"start":{"date-parts":[[2022,7,1]],"date-time":"2022-07-01T00:00:00Z","timestamp":1656633600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Human Gene Therapy"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:p>\n                    Blue cone monochromacy (BCM) is a congenital vision disorder affecting both middle-wavelength (M) and long-wavelength (L) cone photoreceptors of the human retina. BCM results from abolished expression of green and red light-sensitive visual pigments expressed in M- and L-cones, respectively. Previously, we showed that gene augmentation therapy to deliver either human L- or M-opsin rescues dorsal M-opsin dominant cone photoreceptors structurally and functionally in treated M-opsin knockout (\n                    <jats:italic toggle=\"yes\">\n                      Opn1mw\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    ) mice. Although\n                    <jats:italic toggle=\"yes\">\n                      Opn1mw\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    mice represent a disease model for BCM patients with deletion mutations, at the cellular level, dorsal cones of\n                    <jats:italic toggle=\"yes\">\n                      Opn1mw\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    mice still express low levels of S-opsin, which are different from L- and M-cones of BCM patients carrying a congenital opsin deletion. To determine whether BCM cones lacking complete opsin expression from birth would benefit from AAV-mediated gene therapy, we evaluated the outcome of gene therapy, and determined the therapeutic window and longevity of rescue in a mouse model lacking both M- and S-opsin (\n                    <jats:italic toggle=\"yes\">\n                      Opn1mw\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      \/Opn1sw\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    ).\n                  <\/jats:p>\n                  <jats:p>\n                    Our data show that cones of\n                    <jats:italic toggle=\"yes\">\n                      Opn1mw\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      \/Opn1sw\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    mice are viable at younger ages but undergo rapid degeneration. AAV-mediated expression of human L-opsin promoted cone outer segment regeneration and rescued cone-mediated function when mice were injected subretinally at 2 months of age or younger. Cone-mediated function and visually guided behavior were maintained for at least 8 months post-treatment. However, when mice were treated at 5 and 7 months of age, the chance and effectiveness of rescue was significantly reduced, although cones were still present in the retina. Crossing\n                    <jats:italic toggle=\"yes\">\n                      Opn1mw\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      \/Opn1sw\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    mice with proteasomal activity reporter mice (Ub\n                    <jats:sup>G76V<\/jats:sup>\n                    \u2013GFP) did not reveal GFP accumulation in\n                    <jats:italic toggle=\"yes\">\n                      Opn1mw\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      \/Opn1sw\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    cones eliminating impaired degradation of ubiquitinated proteins as stress factor contributing to cone loss. Our results demonstrate that AAV-mediated gene augmentation therapy can rescue cone structure and function in a mouse model with a congenital opsin deletion, but also emphasize the importance that early intervention is crucial for successful therapy.\n                  <\/jats:p>","DOI":"10.1089\/hum.2021.298","type":"journal-article","created":{"date-parts":[[2022,3,11]],"date-time":"2022-03-11T01:58:43Z","timestamp":1646963923000},"page":"708-718","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":14,"title":["Gene Therapy in\n                    <i>\n                      Opn1mw\n                      <sup>\u2212\/\u2212<\/sup>\n                      \/Opn1sw\n                      <sup>\u2212\/\u2212<\/sup>\n                    <\/i>\n                    Mice and Implications for Blue Cone Monochromacy Patients with Deletion Mutations"],"prefix":"10.1177","volume":"33","author":[{"given":"Xiajie","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, College of Medicine, University of Florida, Gainesville, Florida, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emily R.","family":"Sechrest","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, West Virginia University, Morgantown, West Virginia, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diego","family":"Fajardo","sequence":"additional","affiliation":[{"name":"Division of Cellular and Molecular Therapeutics, Department of Pediatrics; University of Florida, Gainesville, Florida, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, College of Medicine, University of Florida, Gainesville, Florida, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank","family":"Dyka","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, College of Medicine, University of Florida, Gainesville, Florida, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yixiao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, College of Medicine, University of Florida, Gainesville, Florida, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8309-7199","authenticated-orcid":false,"given":"Ekaterina","family":"Lobanova","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, College of Medicine, University of Florida, Gainesville, Florida, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shannon E.","family":"Boye","sequence":"additional","affiliation":[{"name":"Division of Cellular and Molecular Therapeutics, Department of Pediatrics; University of Florida, Gainesville, Florida, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wolfgang","family":"Baehr","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Science, University of Utah, Salt Lake City, Utah, USA."},{"name":"Department of Neurobiology and Anatomy, University of Utah, Salt Lake City, Utah, USA."},{"name":"Department of Biology, University of Utah, Salt Lake City, Utah, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9357-0656","authenticated-orcid":false,"given":"Wen-Tao","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, West Virginia University, Morgantown, West Virginia, USA."},{"name":"Department of Biochemistry, West Virginia University, Morgantown, West Virginia, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2022,7,13]]},"reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep28253"},{"key":"e_1_3_5_3_2","first-page":"876","article-title":"Blue cone monochromacy: causative mutations and associated phenotypes","volume":"15","author":"Gardner JC","year":"2009","unstructured":"Gardner JC, , Michaelides M, , Holder GE, et al. 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