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Thomas M. Bosley, Ali Hellani, George L. Spaeth, Jonathan Myers, L. Jay Katz, Marlene Moster, Khaled K. Abu-Amero; OPA1 Expression in Patients with Primary Open Angle Glaucoma. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2409.
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Heterozygous OPA1 mutations are responsible for dominant optic atrophy, and down regulation of OPA1 expression in blood of patients with Leber hereditary optic neuropathy and the 11778 primary LHON mutation may imply that OPA1 levels in mitochondria play a role in this type of spontaneous optic neuropathy as well. Mitochondrial and metabolic abnormalities may put the optic nerve at risk in primary open angle glaucoma (POAG), and this study was designed to provide evidence regarding whether decreased OPA1 expression might be responsible in part for the progressive optic neuropathy of POAG.
Patients were eligible for inclusion if they met standard clinical criteria for POAG, including: age greater than 40 years; intraocular pressure ≥ 21 mm Hg in at least one eye prior to 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. OPA1 expression levels were assessed by real time PCR and compared to expression levels of the β-globulin housekeeping gene. The ratio of OPA1 expression to β-globulin gene expression (OPA1/β-globulin) for POAG patients was compared to that of controls.
Forty-three POAG patients and 27 controls were completely phenotyped with a full ophthalmologic examination and static perimetry. Mean age (POAG 67.0 years; controls 61.8 years) and sex (POAG 26 males/17 females; controls 11/16) were similar for the two groups. Mean OPA1/β-globulin of POAG patients (1.16, S.D. 0.26) was less than that of controls (1.41, S.D. 0.50), and this difference was statistically significant (p≤ 0.021). β-globulin expression alone did not differ between the groups (p≤0.24).
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 and/or progression of POAG.
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