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

Deficiency of ornithine-delta-aminotransferase (OAT) in humans results in g yrate atrophy of the choroid and retina (GA), an autosomal recessive disord er characterized by ornithine accumulation and a progressive chorioretinal degeneration of unknown pathogenesis. To determine whether chronic, systemi c reduction of ornithine can prevent this form of retinal degeneration, we used an arginine-restricted diet to maintain long term reduction of ornithi ne 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 ami no acids, electroretinograms, and retinal histologic and ultrastructural st udies. We found that an arginine-restricted diet substantially reduces plas ma 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 CA and that restorati on of OAT activity in retina is not required for effective treatment of CA.