GYRATE atrophy (GA) is a severe human recessive eye disease resulting in progressive loss of vision due to chorioretinal degeneration. The disorder is associated with a deficiency of the mitochondrial matrix enzyme, ornithi delta-aminotransferase (OAT), which catalyzes the interconversion of ornithine and alpha-ketoglutarate to delta-pyrroline-5'-carboxylate and glutamate. GA patients with activity have 10 to 20-fold higher levels of plasma ornithine as compared with controls. Dietary and specific hormonal administration in rats and mice have been shown to modulate the regulation of this enzyme in different tissues, suggesting OAT's important physiologic role in vivo. To test this hypothesis and to find out whether ornithine delta-aminotransferase could be a common mediator for retinal cell growth, we produced two transgenic lines, expressing the human OAT gene in strains of mice normally exhibiting a progressive retinal degeneration. Here we show that transgenic mice expressing human ornithine delta-aminotransferase exhibit less severe retinal degeneration than control mice littermates.
