Evidence for association of endothelial nitric oxide synthase gene in subjects with glaucoma and a history of migraine.

PURPOSE: There is evidence to suggest that vasospasm and vascular dysregulation play a role in the etiology of glaucoma. This effect may be particularly relevant in patients with glaucoma who have a history of migraine or vasospastic tendencies. This study was conducted to investigate the role of genes with products that regulate blood flow to ocular tissues. The candidate genes were the two isoforms of nitric oxide synthase (NOS), NOS3 and -2A, and endothelin (ET)-l. The frequency of the T786C mutation in NOS3 was also examined. METHODS: DNA was obtained from 58 patients with primary open-angle glaucoma (POAG), 76 with normal tension glaucoma (NTG), and 38 control subjects. Polymerase chain reactions (PCR) were used to compare the frequency of the alleles between the subjects with glaucoma and the control subjects and the subjects with glaucoma with vasospasm or migraine. The PCR product was sequenced to identify the frequency of the T786C mutation. RESULTS: The distribution of the NOS3 repeat alleles in subjects with glaucoma and control subjects just failed to reach statistical significance (P = 0.06). The distribution in subjects with NTG or POAG did not differ significantly. A significant difference was found (P < 0.001) in the distribution of allele frequencies of the NOS3 marker in subjects who had glaucoma with migraine versus control subjects. There were no differences in the distribution of the NOS2A or ET-1 markers between the subjects with glaucoma and the control subjects. CONCLUSIONS: This study provides evidence of an association between the NOS3 gene and subjects with glaucoma who have a history of migraine. Unlike in other studies, no evidence was found of an association between ET-1 and glaucoma.

Peripheral resolution for achromatic and SWS gratings in early to moderate glaucoma and the implications for selective ganglion cell density loss.

PURPOSE: To investigate whether there is significant selective reduction in short-wavelength-sensitive (SWS) ganglion cell density in early to moderate glaucoma. METHODS: Peripheral achromatic resolution acuity (an indirect measure of the underlying midget ganglion cell density) and peripheral chromatic resolution acuity under conditions of blue cone isolation (an indirect measure of the underlying small bistratified ganglion cell density) were measured at 13 degrees eccentricity in four oblique meridians in 15 eyes (mean age, 64.6 +/- 9.6 years) with early to moderate glaucoma. The results from the subjects with glaucoma were compared with those in a group of 17 age-matched normal eyes (mean age, 62.5 +/- 6.6 years). RESULTS: Mean achromatic resolution acuity across the four locations was significantly lower in the subjects with glaucoma than in the normal subjects (2.92 vs. 4.01 cyc/deg). Mean chromatic resolution acuity across the four locations was also significantly lower in the subjects with glaucoma than the normal subjects (0.78 vs. 0.99 cyc/deg). There was no selective loss of mean SWS acuity in the subjects with glaucoma. Individual location analysis revealed that the chromatic-achromatic resolution ratio was not significantly different in the subjects with glaucoma who had early glaucomatous damage when compared with the normal subjects. The chromatic-achromatic resolution ratio was lower than normal at certain locations in certain individuals with early glaucoma. CONCLUSIONS: The results indicate that there is no evidence of significant selective reduction in global SWS ganglion cell density in early to moderate glaucoma. However, there may be selective loss of SWS ganglion cell density at individual locations in individual eyes.