{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T16:23:01Z","timestamp":1781108581741,"version":"3.54.1"},"reference-count":52,"publisher":"National Academy of Sciences","issue":"4","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2001,2,13]]},"abstract":"<jats:p>\n                    Isotretinoin (13\n                    <jats:italic>-cis<\/jats:italic>\n                    retinoic acid) is\n frequently prescribed for severe acne [Peck, G. L., Olsen,\n T. G., Yoder, F. W., Strauss, J. S., Downing, D.\n T., Pandya, M., Butkus, D. &amp; Arnaud-Battandier, J. (1979)\n                    <jats:italic>N. Engl. J. Med.<\/jats:italic>\n                    300, 329\u2013333] but can\n impair night vision [Fraunfelder, F. T., LaBraico, J. M. &amp;\n Meyer, S. M. (1985)\n                    <jats:italic>Am. J. Ophthalmol.<\/jats:italic>\n                    100,\n 534\u2013537] shortly after the beginning of therapy [Shulman, S. R.\n (1989)\n                    <jats:italic>Am. J. Public Health<\/jats:italic>\n                    79, 1565\u20131568]. As rod\n photoreceptors are responsible for night vision, we administered\n isotretinoin to rats to learn whether night blindness resulted from rod\n cell death or from rod functional impairment. High-dose isotretinoin\n was given daily for 2 months and produced systemic toxicity, but this\n caused no histological loss of rod photoreceptors, and rod-driven\n electroretinogram amplitudes were normal after prolonged dark\n adaptation. Additional studies showed, however, that even a single dose\n of isotretinoin slowed the recovery of rod signaling after exposure to\n an intense bleaching light, and that rhodopsin regeneration was\n markedly slowed. When only a single dose was given, rod function\n recovered to normal within several days. Rods and cones both showed\n slow recovery from bleach after isotretinoin in rats and in mice. HPLC\n analysis of ocular retinoids after isotretinoin and an intense bleach\n showed decreased levels of rhodopsin chromophore, 11\n                    <jats:italic>-cis<\/jats:italic>\n                    retinal, and the accumulation of the biosynthetic intermediates,\n 11-\n                    <jats:italic>cis<\/jats:italic>\n                    and all\n                    <jats:italic>-trans<\/jats:italic>\n                    retinyl esters.\n Isotretinoin was also found to protect rat photoreceptors from\n light-induced damage, suggesting that strategies of altering retinoid\n cycling may have therapeutic implications for some forms of retinal and\n macular degeneration.\n                  <\/jats:p>","DOI":"10.1073\/pnas.98.4.1835","type":"journal-article","created":{"date-parts":[[2012,7,26]],"date-time":"2012-07-26T19:12:10Z","timestamp":1343329930000},"page":"1835-1840","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":116,"title":["Inhibition of the visual cycle\n                    <i>in vivo<\/i>\n                    by 13\n                    <i>-cis<\/i>\n                    retinoic acid protects from light damage and provides a mechanism for night blindness in isotretinoin therapy"],"prefix":"10.1073","volume":"98","author":[{"given":"Paul A.","family":"Sieving","sequence":"first","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences,\r Center for Bioengineering Research,\r Program in Neuroscience, and Department of Biological\r Chemistry, W. K. Kellogg Eye Center, University of Michigan\r Medical School, 1000 Wall Street, Ann Arbor, MI 48105"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prem","family":"Chaudhry","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences,\r Center for Bioengineering Research,\r Program in Neuroscience, and Department of Biological\r Chemistry, W. K. Kellogg Eye Center, University of Michigan\r Medical School, 1000 Wall Street, Ann Arbor, MI 48105"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mineo","family":"Kondo","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences,\r Center for Bioengineering Research,\r Program in Neuroscience, and Department of Biological\r Chemistry, W. K. Kellogg Eye Center, University of Michigan\r Medical School, 1000 Wall Street, Ann Arbor, MI 48105"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Provenzano","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences,\r Center for Bioengineering Research,\r Program in Neuroscience, and Department of Biological\r Chemistry, W. K. Kellogg Eye Center, University of Michigan\r Medical School, 1000 Wall Street, Ann Arbor, MI 48105"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences,\r Center for Bioengineering Research,\r Program in Neuroscience, and Department of Biological\r Chemistry, W. K. Kellogg Eye Center, University of Michigan\r Medical School, 1000 Wall Street, Ann Arbor, MI 48105"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Carlson","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences,\r Center for Bioengineering Research,\r Program in Neuroscience, and Department of Biological\r Chemistry, W. K. Kellogg Eye Center, University of Michigan\r Medical School, 1000 Wall Street, Ann Arbor, MI 48105"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald A.","family":"Bush","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences,\r Center for Bioengineering Research,\r Program in Neuroscience, and Department of Biological\r Chemistry, W. K. Kellogg Eye Center, University of Michigan\r Medical School, 1000 Wall Street, Ann Arbor, MI 48105"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debra A.","family":"Thompson","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences,\r Center for Bioengineering Research,\r Program in Neuroscience, and Department of Biological\r Chemistry, W. K. 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