Glaucoma is the second leading cause of permanent blindness in the United States and other developed countries, and the single leading cause of blindness among African-Americans. The understanding of glaucoma at the molecular level has the potential to markedly improve diagnosis and treatment of this disorder. Up to 50% of cases of glaucoma have been reported to be familial. Some cases of glaucoma are well documented to be inherited as autosomal dominant and autosomal recessive disorders, while other cases are thought to be multifactorial. In this project, our approach will be to use genetic linkage analysis and positional cloning strategies to investigate a subset of glaucoma that shows monogenic inheritance. We will map and identify genes involved in three forms of inherited glaucoma: Juvenile primary open angle glaucoma, primary open angle glaucoma with iris hypoplasia, and primary infantile glaucoma. To do this, we will take advantage of large families with autosomal dominant inheritance. In addition, we will utilize a cell line from a patient with infantile glaucoma to clone a 6:13 translocation breakpoint thought to be at the site of a gene causing this form of glaucoma. We will also test the involvement of these loci in the most common form of glaucoma (adult primary open angle) by genetic association studies in the Black and Caucasian populations. We contend that identification of genes that cause Mendelian forms of glaucoma will improve our understanding of the pathogenic processes involved in this class of diseases. We also propose to prospectively study two families with juvenile primary open angle glaucoma (linked to chromosome 1q) to characterize the earliest stages of the disease and to determine the response of this disorder to early institution of standard medical therapy. Data obtained from this aspect of the project will make a significant impact on the management of patients with juvenile primary open angle glaucoma.
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