Modification of ocular defects in mouse developmental glaucoma models by tyrosinase.

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Science (New York, N.Y.), ISSN: 1095-9203, Vol: 299, Issue: 5612, Page: 1578-81

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Libby, Richard T; Smith, Richard S; Savinova, Olga V; Zabaleta, Adriana; Martin, Janice E; Gonzalez, Frank J; John, Simon W M
American Association for the Advancement of Science (AAAS)
article description
Mutations in the cytochrome P450 family 1, subfamily B, polypeptide 1 (CYP1B1) gene are a common cause of human primary congenital glaucoma (PCG). Here we show that Cyp1b1-/- mice have ocular drainage structure abnormalities resembling those reported in human PCG patients. Using Cyp1b1-/- mice, we identified the tyrosinase gene (Tyr) as a modifier of the drainage structure phenotype, with Tyr deficiency increasing the magnitude of dysgenesis. The severe dysgenesis in eyes lacking both CYP1B1 and TYR was alleviated by administration of the tyrosinase product dihydroxyphenylalanine (l-dopa). Tyr also modified the drainage structure dysgenesis in mice with a mutant Foxc1 gene, which is also involved in PCG. These experiments raise the possibility that a tyrosinase/l-dopa pathway modifies human PCG, which could open new therapeutic avenues.