Developmental Glaucoma
In developmental glaucomas, abnormal formation of the ocular drainage structures in the angle of the eye is a cause of IOP elevation. We have characterized angle malformation genes, including the forkhead transcription factor (Foxc2), bone morphogenetic protein (Bmp4), and collagen type IV alpha 1 (Col4a1). We have also studied mice with mutations in the genes for cytochrome P450 1b1 (Cyp1b1) and forkhead box transcription factor C1 (Foxc1), which cause human developmental glaucoma. Because of extensive variability in the human disease, we used mice to identify a modifier gene that alters ocular abnormalities due to mutations in Cyp1b1 and Foxc1. Genetic deficiency of tyrosinase exacerbates defects in both Cyp1b1 and Foxc1 mutant mice. Tyrosinase provides L-DOPA that protects against angle malformation. Future work will be aimed at further understanding the role of L-DOPA in ocular development and glaucoma, evaluating if and how dietary DOPA modulates the severity of human glaucoma, and identifying further genes that modify the phenotypic effects of Cyp1b1 mutations.
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