{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:47:59Z","timestamp":1791348479500,"version":"4.3.1"},"reference-count":25,"publisher":"National Academy of Sciences","issue":"49","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2007,12,4]]},"abstract":"<jats:p>\n                    Highly abundant short-chain alcohol dehydrogenases (RDHs) in the retina were assumed to be involved in the recycling of 11-\n                    <jats:italic>cis<\/jats:italic>\n                    -retinal chromophore in the visual cycle. Mutations in human RDH genes are associated with\n                    <jats:italic>Fundus albipunctatus<\/jats:italic>\n                    , a mild form of night blindness (\n                    <jats:italic>RDH5<\/jats:italic>\n                    ) and an autosomal recessive, childhood-onset severe retinal dystrophy (\n                    <jats:italic>RDH12<\/jats:italic>\n                    ).\n                    <jats:italic>Rdh12<\/jats:italic>\n                    knockout mice were found to be susceptible to light-induced photoreceptor apoptosis, whereas\n                    <jats:italic>Rdh5<\/jats:italic>\n                    and\n                    <jats:italic>Rdh8<\/jats:italic>\n                    knockout mice displayed only delayed dark adaptation. However, each knockout mouse eventually regenerated normal levels of visual pigments, suggesting that RDHs compensate for each other in the visual cycle. Here, we established RDH double knockout (\n                    <jats:italic>Rdh8<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <jats:italic>Rdh12<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ) and triple knockout (\n                    <jats:italic>Rdh5<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <jats:italic>Rdh8<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <jats:italic>Rdh12<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ) mice generated on various genetic backgrounds including a rod \u03b1-transducin knockout to test cone function. RDH activity was severely reduced in\n                    <jats:italic>Rdh8<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    Rdh12\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    retina extracts, whereas\n                    <jats:italic>Rdh8<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    RDH activity was intermediate and\n                    <jats:italic>Rdh12<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    RDH activity was reduced only slightly. Surprisingly, all multiple knockout mice produced sufficient amounts of the chromophore to regenerate rhodopsin and cone pigments\n                    <jats:italic>in vivo<\/jats:italic>\n                    . Three-month-old\n                    <jats:italic>Rdh8<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <jats:italic>Rdh12<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice characteristically displayed a slowly progressing rod\u2013cone dystrophy accompanied by accumulation of\n                    <jats:italic>N<\/jats:italic>\n                    -retinylidene-\n                    <jats:italic>N<\/jats:italic>\n                    -retinylethanolamine (A2E), a toxic substance known to contribute to retinal degeneration. A2E accumulation and retinal degeneration were prevented by application of retinylamine, a potent retinoid cycle inhibitor. The results suggest that RDH8 and RDH12 are dispensable in support of the visual cycle but appear to be key components in clearance of free all-\n                    <jats:italic>trans<\/jats:italic>\n                    -retinal, thereby preventing A2E accumulation and photoreceptor cell death.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0707477104","type":"journal-article","created":{"date-parts":[[2007,11,28]],"date-time":"2007-11-28T20:45:29Z","timestamp":1196282729000},"page":"19565-19570","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":114,"title":["Redundant and unique roles of retinol dehydrogenases in the mouse retina"],"prefix":"10.1073","volume":"104","author":[{"given":"Akiko","family":"Maeda","sequence":"first","affiliation":[{"name":"*Department of Pharmacology, Case Western Reserve University, Cleveland, OH 44106-4965; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadao","family":"Maeda","sequence":"additional","affiliation":[{"name":"*Department of Pharmacology, Case Western Reserve University, Cleveland, OH 44106-4965; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyu","family":"Sun","sequence":"additional","affiliation":[{"name":"*Department of Pharmacology, Case Western Reserve University, Cleveland, OH 44106-4965; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Houbin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Departments of \u2020Ophthalmology and Visual Sciences,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Baehr","sequence":"additional","affiliation":[{"name":"Departments of \u2020Ophthalmology and Visual Sciences,"},{"name":"Biology, and"},{"name":"Neurobiology and Anatomy, University of Utah, Salt Lake City, UT 84132"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krzysztof","family":"Palczewski","sequence":"additional","affiliation":[{"name":"*Department of Pharmacology, Case Western Reserve University, Cleveland, OH 44106-4965; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2007,12,4]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.75.103004.142743"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.47.120505.105225"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.15.11034"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M208882200"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M413172200"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.34.21790"},{"key":"e_1_3_3_7_2","first-page":"3365","volume":"43","author":"Wu BX","year":"2002","unstructured":"BX Wu, Y Chen, J Fan, B Rohrer, RK Crouch, JX Ma Invest Ophthalmol Vis Sci 43, 3365\u20133372 (2002).","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M501757200"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M304969200"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1394"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1086\/424889"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M608375200"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01486-06"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M004488200"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi9524068"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.250478897"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0030347"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0503318102"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.3.1107"},{"key":"e_1_3_3_20_2","first-page":"1685","volume":"42","author":"Mata NL","year":"2001","unstructured":"NL Mata, RT Tzekov, X Liu, J Weng, DG Birch, GH Travis Invest Ophthalmol Vis Sci 42, 1685\u20131690 (2001).","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.20.12.4275-4287.2000"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M610369200"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6989(91)90069-H"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M104949200"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M302536200"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0707477104","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T16:38:13Z","timestamp":1649781493000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0707477104"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,12,4]]},"references-count":25,"journal-issue":{"issue":"49","published-print":{"date-parts":[[2007,12,4]]}},"alternative-id":["10.1073\/pnas.0707477104"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0707477104","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,12,4]]},"assertion":[{"value":"2007-08-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2007-12-04","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}