Nuclear and mitochondrial analysis of patients with primary angle-closure glaucoma

PURPOSE. Certain types of glaucoma are linked to nuclear genetic mutations or to mitochondrial disturbances. In this study, patients with primary angle-closure glaucoma (PACG) were examined for mutations in nuclear genes reported to be associated with glaucoma and for possible mitochondrial abnormalities. METHODS. In patients with PACG, the nuclear genes MYOC, OPTN, CYP1B1, WDR36, OPA1, and OPA3 were sequenced, the entire mitochondrial (mt) DNA coding region was sequenced, relative mtDNA content was measured, and mitochondrial respiratory activity (MRA) was assessed. RESULTS. No novel or previously reported mutations were present in the nuclear genes MYOC, OPTN, CYP1B1, WDR36, OPA1, and OPA3 in 29 patients with PACG. Four (13.8%) patients had potentially pathologic mtDNA nucleotide changes not found in control subjects. The patients with PACG did not differ significantly from the control subjects in relative mitochondrial content and had only a small decrease in MRA (2.4%) of indeterminate significance. CONCLUSIONS. These Middle Eastern patients with PACG had no mutations in nuclear genes associated with other types of glaucoma or inherited optic neuropathies. Mitochondrial abnormalities were minimal, and the overall pattern of those abnormalities was distinctly different from that of Leber hereditary optic neuropathy, nonarteritic ischemic optic neuropathy, primary open-angle glaucoma, and optic neuritis. These results are consistent with the hypothesis that anatomic factors may be more important determinants for PACG than the genetic and mitochondrial factors evaluated here.