title: Correction of ornithine accumulation prevents retinal degeneration in a mouse model of gyrate atrophy of the choroid and retina.
abstract: Deficiency of ornithine-delta-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 (Oat(-/-)) 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 Oat(-/-). 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.
authors.affiliation: Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: T
authors.initials: T
authors.lastname: Wang
authors.forename: G
authors.initials: G
authors.lastname: Steel
authors.forename: A H
authors.initials: AH
authors.lastname: Milam
authors.forename: D
authors.initials: D
authors.lastname: Valle
mesh_terms: D000596:Amino Acids / Q000097:blood; D000818:Animals; D001120:Arginine / Q000008:administration & dosage*; D002829:Choroid / Q000473:pathology; D004195:Disease Models, Animal; D004596:Electroretinography; D015799:Gyrate Atrophy / Q000150:complications / Q000178:diet therapy* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009952:Ornithine / Q000378:metabolism*; D009953:Ornithine-Oxo-Acid Transaminase / Q000172:deficiency*; D012160:Retina / Q000473:pathology; D012162:Retinal Degeneration / Q000178:diet therapy / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*
chemical_list: D000596:Amino Acids; D001120:Arginine; D009952:Ornithine; D009953:Ornithine-Oxo-Acid Transaminase