MOLECULAR SCREENING METHODS FOR DIFFERENT TYPES OF GLAUCOMA

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Glaucoma represents a group of inherited eye disorders that collectively accounts for 3% of all blindness in the US and worldwide. In recent years, the chromosomal locations of seven glaucoma loci have been identified (five of which were identified by us and two by other groups). Further, we and another group recently described the first mutations in two independent genes, namely that encoding Cytochrome P4501B1 (CYP1B1) and the Trabecular Meshwork -Induced Glucocorticoid Response protein (TIGR), in families segregating for primary congenital and primary open angle types of glaucoma, respectively. Since then, the role of these two genes in the etiology of these two types of glaucoma has been confirmed by other investigators and in other populations. To date, we have identified 16 novel CYP1B1 mutations in familial and sporadic cases with primary congenital glaucoma and six new TIGR mutations in families with primary open angle glaucoma. Given these findings, we believe it is now feasible to use these molecular methods to identify subjects at risk for these conditions before the irreversible optic nerve damage of glaucoma has occurred. Therefore, the specific aims of this project are: 1) To identify, ascertain, and clinically examine a large sample of glaucoma patients (N = 500) recruited from ophthalmology practices in Connecticut; 2) To obtain blood or buccal tissue samples from these individuals and to extract and bank the DNA; 3) To systematically screen DNA from these patients for the two genes, CYP1B1 and TIGR, which are known to be of etiologic significance in glaucoma; 4) To screen DNA from these patients for mutations in other genes that are subsequently identified as being of etiologic significance in glaucoma; and 5) To correlate the type of mutation (genotype) with the clinical data (phenotype) in affected subjects. The GCRC will be instrumental in the identification, ascertainment and clinical examination of these individuals; in sample collection and processing; and in mutation screening, which is based upon ongoing work in our laboratory and the laboratories of other investigators who are active in this rapidly- developing area of research.