Molecular genetic studies of primary open angle and angle closure glaucoma

Glaucoma, a group of heterogeneous optic neuropathies characterized by progressive visual field loss, is the leading cause of irreversible blindness worldwide. The condition has a substantial heritable basis, as illustrated by the numerous loci and genes identified to date, and the large proportion of patients having a family history. Categorized according to the anatomy of the anterior chamber angle, there are 2 main forms of glaucoma, primary open angle glaucoma (POAG) and primary angle closure glaucoma (PACG). The first half of the thesis describes the molecular genetic study of POAG, while the latter deals with PACG. Primary open angle glaucoma (POAG) accounts for most glaucoma in Caucasian and Afro-Caribbean populations. The condition is classified according to the presence of elevated intraocular pressure (IOP) into hightension glaucoma (HTG) or normal tension glaucoma (NTG). OPA1, the gene responsible for autosomal dominant optic atrophy represents an excellent candidate gene for POAG (in particular NTG). Single nucleotide polymorphisms on intervening sequence (IVS) 8 of the OPAlgens (genotype IVS 8 +4 C/T; +32 T/C) were found to be strongly associated with a fifth of NTG cases and may be a marker for disease association, providing the first evidence of an association between OPA1 and NTG. However this OPA1 genotype was not found to be significantly associated with HTG. Further work did not detect a significant difference in a range of phenotypic features in NTG patients with and without these OPA1 polymorphisms, suggesting that