Gyrate Atrophy of the Choroid and Retina

François, J.

doi:10.1159/000308842

Cited by 9 publications

(6 citation statements)

References 16 publications

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“…[11][12][13] Dietary restriction of arginine has been shown to prevent (but not reverse) retinal degeneration in OAT-deficient mice. 14 In humans, the impacts of this treatment have been more varied, with results ranging from visual improvement, [15][16][17] marked delay of, [18][19][20][21] modest delay of, 22,23 to no discernable bearing on 24 the progression of ocular symptoms.…”

Section: Introductionmentioning

confidence: 99%

Auxotrophy-Based Detection of Hyperornithinemia in Mouse Blood and Urine

Palanza

Nesta

Tumu

et al. 2016

Journal of Inborn Errors of Metabolism and Screening

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Gyrate atrophy of the choroid and retina (GACR) is a hereditary form of progressive blindness caused by homozygosity for lossof-function mutations in the ornithine aminotransferase gene (Oat). The high levels of circulating ornithine that lead to ophthalmic symptoms in young adults are also displayed by 2 ornithine aminotransferase (OAT)-deficient mouse models of GACR. Here, we have developed an inexpensive and quantitative bacteria-based test for detecting hyperornithinemia in blood or urine samples from these mutant mice, a test that we suggest could be used to facilitate the identification and treatment of OAT-deficient humans before the onset of visual impairment.Keywords argE mutant E coli, gyrate atrophy of the choroid and retina, ornithine biosensor, metabolic screening, animal models of human disease

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Section: Introductionmentioning

confidence: 99%

Auxotrophy-Based Detection of Hyperornithinemia in Mouse Blood and Urine

Palanza

Nesta

Tumu

et al. 2016

Journal of Inborn Errors of Metabolism and Screening

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“…Clinically, GA patients initially develop myopia and reduced night vision, followed by gradual reduction in peripheral vision with constriction of the visual fields, leading to complete loss of vision at around the fourth to fifth decade of life (2)(3)(4). The presence of numerous sharply demarcated circular areas with hyperpigmented margins in the anterior to midperipheral retina is the earliest diagnostic funduscopic feature of GA. Over time, these lesions increase in number and size, coalesce, and spread from the peripheral to the central fundus.…”

Section: Introductionmentioning

confidence: 99%

A mouse model of gyrate atrophy of the choroid and retina. Early retinal pigment epithelium damage and progressive retinal degeneration.

Wang¹,

Milam²,

Steel³

et al. 1996

J. Clin. Invest.

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Gyrate atrophy (GA) of the choroid and retina is a blinding chorioretinal degeneration caused by deficiency of ornithine ␦ -aminotransferase (OAT). The phenotype of GA is characterized by progressive concentric reduction of the visual fields and ornithine accumulation. To understand better the pathogenesis of GA and to develop a model to test therapeutic strategies, we produced an OAT-deficient mouse by gene targeting. Like human GA patients, adult OAT-deficient mice exhibit chronic hyperornithinemia to levels 10-15-fold above normal and massive ornithinuria. Slowly progressive retinal degeneration is reflected by a gradual decline in electroretinogram amplitudes over the first 12 mo of life. At 2 mo, the retinal pigment epithelium is histologically normal, but electron microscopy reveals sporadic degeneration of scattered pigment epithelial cells.

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“…GA patients present in childhood with myopia followed by the development of night blindness, cataracts, and progressive constriction of vision fields, leading to blindness in the fourth to fifth decade (3)(4)(5). These visual symptoms are associated with the development of sharply demarcated, nummular areas of chorioretinal atrophy initially occurring in the midperiphery of the ocular fundus.…”

mentioning

confidence: 99%

Correction of ornithine accumulation prevents retinal degeneration in a mouse model of gyrate atrophy of the choroid and retina

Wang

Steel

Milam

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

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Deficiency of ornithine-␦-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 argininerestricted 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 argininerestricted 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.

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Gyrate Atrophy of the Choroid and Retina

Cited by 9 publications

References 16 publications

Auxotrophy-Based Detection of Hyperornithinemia in Mouse Blood and Urine

Auxotrophy-Based Detection of Hyperornithinemia in Mouse Blood and Urine

A mouse model of gyrate atrophy of the choroid and retina. Early retinal pigment epithelium damage and progressive retinal degeneration.

Correction of ornithine accumulation prevents retinal degeneration in a mouse model of gyrate atrophy of the choroid and retina

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