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Abstract #46051 Published in IGR 13-2
Down-regulation of OPA1 in patients with primary open angle glaucoma
Bosley TM; Hellani A; Spaeth GL; Myers J; Katz LJ; Moster MR; Milcarek B; Abu-Amero KKMolecular Vision 2011; 17: 1074-1079
Purpose: Heterozygous optic atrophy type1 (OPA1) mutations are responsible for dominant optic atrophy, and the down regulation of OPA1 expression in patients with Leber hereditary optic neuropathy may imply that Opa1 protein levels in mitochondria play a role in other spontaneous optic neuropathies as well. Mitochondrial and metabolic abnormalities may put the optic nerve at risk in primary open angle glaucoma (POAG), and this preliminary study was designed to investigate whether altered OPA1 expression might be present in the progressive optic neuropathy of POAG. Methods: Patients were eligible for inclusion if they met standard clinical criteria for POAG, including age greater than 40 years, intraocular pressure (greater-than or equal to) 21 mmHg in at least one eye before treatment, normal-appearing anterior chamber angles bilaterally on gonioscopy, and optic nerve injury characteristic of POAG. RNA was extracted from leukocytes and converted to cDNA by reverse transcriptase enzyme, and real time PCR was used to assess expression levels of OPA1 and the (beta)-globulin (HBB) housekeeping gene. The ratio of OPA1 expression to HBB expression (OPA1/HBB) for POAG patients was compared to that of controls and to clinical characteristics of POAG patients. Results: Forty-three POAG patients and 27 controls were completely phenotyped with a full ophthalmologic examination and static perimetry. Mean age (POAG 67.9 years; controls 61.8 years) and sex (POAG 26 males/17 females; controls 11/16) were similar for the two groups. Mean OPA1/HBB of POAG patients (1.16, SD 0.26) was 18% lower than controls (1.41, SD 0.50), and this difference was statistically significant (p(less-than or equal to)0.021). OPA1 expression differed between the groups (p(less-than or equal to)0.037), but HBB expression did not differ (p(less-than or equal to)0.24). OPA1/HBB was not correlated with any clinical feature of POAG patients. Conclusions: Transcriptional analysis of peripheral blood leucocytes is a limited model system for studying the consequences of mitochondrial abnormalities in the optic nerve. Nevertheless, OPA1 is known to affect mitochondrial stability and has now been implicated in several spontaneous optic neuropathies. Decreased OPA1 expression in POAG patients is another indication that mitochondrial function, and possibly mitochondrially-induced apoptosis, may play a role in the development of POAG.
K. K. Abu-Amero. Ophthalmic Genetics Laboratory, Department of Ophthalmology, College of Medicine, King Saud University, P. O. Box 245, Riyadh 11411, Saudi Arabia. Email: abuamero@gmail.com
Classification:
3.4.2 Gene studies (Part of: 3 Laboratory methods > 3.4 Molecular genetics)
3.5 Molecular biology incl. SiRNA (Part of: 3 Laboratory methods)