{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T14:55:17Z","timestamp":1781103317412,"version":"3.54.1"},"reference-count":38,"publisher":"National Academy of Sciences","issue":"3","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2000,2]]},"abstract":"<jats:p>\n                    Deficiency of ornithine-\u03b4-aminotransferase (OAT) in humans results in gyrate atrophy of the choroid and retina (GA), an autosomal recessive disorder characterized by ornithine accumulation and a progressive chorioretinal degeneration of unknown pathogenesis. To determine whether chronic, systemic reduction of ornithine can prevent this form of retinal degeneration, we used an arginine-restricted diet to maintain long term reduction of ornithine in a mouse model of OAT-deficiency (\n                    <jats:italic>Oat<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ) produced by gene targeting. We evaluated the mice over a 12-month period by measurement of plasma amino acids, electroretinograms, and retinal histologic and ultrastructural studies. We found that an arginine-restricted diet substantially reduces plasma ornithine levels and completely prevents retinal degeneration in\n                    <jats:italic>Oat<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    . This result indicates that ornithine accumulation is a necessary factor in the pathophysiology of the retinal degeneration in GA and that restoration of OAT activity in retina is not required for effective treatment of GA.\n                  <\/jats:p>","DOI":"10.1073\/pnas.97.3.1224","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:38:21Z","timestamp":1027679901000},"page":"1224-1229","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":74,"title":["Correction of ornithine accumulation prevents retinal degeneration in a mouse model of gyrate atrophy of the choroid and retina"],"prefix":"10.1073","volume":"97","author":[{"given":"Tao","family":"Wang","sequence":"first","affiliation":[{"name":"Howard Hughes Medical Institute and Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205; and Scheie Eye Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary","family":"Steel","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute and Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205; and Scheie Eye Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann H.","family":"Milam","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute and Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205; and Scheie Eye Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Valle","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute and Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205; and Scheie Eye Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2000,2]]},"reference":[{"key":"e_1_3_3_1_2","first-page":"202","volume":"26","author":"Jacobsohn E","year":"1888","unstructured":"E Jacobsohn Klin Monatsbl Augenheilkd 26, 202\u2013206 (1888).","journal-title":"Klin Monatsbl Augenheilkd"},{"key":"e_1_3_3_2_2","first-page":"1147","volume-title":"The Metabolic and Molecular Bases of Inherited Disease","author":"Valle D","year":"1995","unstructured":"D Valle, O Simell The Metabolic and Molecular Bases of Inherited Disease, eds C Scriver, A Beaudet, W Sly, D Valle (McGraw\u2013Hill, New York), pp. 1147\u20131185 (1995)."},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-6420(81)35031-3"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-6420(85)34022-8"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1159\/000308842"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)50731-1"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)68219-5"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.83.5.1203"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1089\/dna.1.1986.5.493"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0304-4165(76)90188-4"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-199009000-00022"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-199804000-00002"},{"key":"e_1_3_3_13_2","first-page":"1457","volume":"19","author":"Hayakasa S","year":"1980","unstructured":"S Hayakasa, T Shiono, Y Takaku, K Mizuno Invest Ophthalmol 19, 1457\u20131460 (1980).","journal-title":"Invest Ophthalmol"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00964382"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/0305-0491(87)90075-7"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-6420(81)35035-0"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-6420(81)35033-7"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(78)92211-0"},{"key":"e_1_3_3_19_2","first-page":"81","volume":"8","author":"Ramesh V","year":"1991","unstructured":"V Ramesh, J Gusella, V Shih Mol Biol Med 8, 81\u201393 (1991).","journal-title":"Mol Biol Med"},{"key":"e_1_3_3_20_2","first-page":"616","volume":"56","author":"Michaud J","year":"1995","unstructured":"J Michaud, G A Mitchell, G N Thompson, L C Brody, G Steel, G Fontaine, K Schappert, C G Keith, D Valle Am J Hum Genet 56, 616\u2013622 (1995).","journal-title":"Am J Hum Genet"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1159\/000181428"},{"key":"e_1_3_3_22_2","first-page":"749","volume":"93","author":"Yatziv S","year":"1979","unstructured":"S Yatziv, M Statter, S Merin J Lab Clin Med 93, 749\u2013757 (1979).","journal-title":"J Lab Clin Med"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198104093041503"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.69.4.283"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI109680"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7444439"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.1991.01080110075039"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-6420(81)35029-5"},{"key":"e_1_3_3_29_2","first-page":"209","volume":"18","author":"Berson E L","year":"1982","unstructured":"E L Berson, A H Hanson, B Rosner, V E Shih Birth Defects Orig Artic Ser 18, 209\u2013218 (1982).","journal-title":"Birth Defects Orig Artic Ser"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-6420(87)33269-5"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1755-3768.1987.tb08499.x"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1095-185"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118730"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-9525(98)01402-4"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(81)92858-0"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9394(14)76892-8"},{"key":"e_1_3_3_37_2","first-page":"1242","volume":"29","author":"Hamasaki D I","year":"1988","unstructured":"D I Hamasaki, R D Dix, S S Atherton Invest Ophthal Visual Sci 29, 1242\u20131254 (1988).","journal-title":"Invest Ophthal Visual Sci"},{"key":"e_1_3_3_38_2","first-page":"1135","volume":"25","author":"Korte G E","year":"1984","unstructured":"G E Korte, V Reppucci, P Henkind Invest Ophthalmol Visual Sci 25, 1135\u20131145 (1984).","journal-title":"Invest Ophthalmol Visual Sci"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.97.3.1224","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T17:48:17Z","timestamp":1649872097000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.97.3.1224"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,2]]},"references-count":38,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2000,2]]}},"alternative-id":["10.1073\/pnas.97.3.1224"],"URL":"https:\/\/doi.org\/10.1073\/pnas.97.3.1224","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2000,2]]},"assertion":[{"value":"1999-09-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2000-02-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}