Down-regulation of OPA1 in patients with primary open angle glaucoma

[摘要] Purpose: Heterozygous optic atrophytype1 (OPA1) mutations are responsible for dominant opticatrophy, and the down regulation of OPA1 expression in patientswith Leber hereditary optic neuropathy may imply that Opa1 proteinlevels in mitochondria play a role in other spontaneous opticneuropathies as well. Mitochondrial and metabolic abnormalities may putthe optic nerve at risk in primary open angle glaucoma (POAG), and thispreliminary study was designed to investigate whether altered OPA1expression might be present in the progressive optic neuropathy ofPOAG. Methods: Patients were eligible forinclusion if they met standard clinical criteria for POAG, includingage greater than 40 years, intraocular pressure ≥ 21 mmHg in atleast one eye before treatment, normal-appearing anterior chamberangles bilaterally on gonioscopy, and optic nerve injury characteristicof POAG. RNA was extracted from leukocytes and converted to cDNA byreverse transcriptase enzyme, and real time PCR was used to assessexpression levels of OPA1 and the β-globulin (HBB)housekeeping gene. The ratio of OPA1 expression to HBBexpression (OPA1/HBB) for POAG patients was compared to that ofcontrols and to clinical characteristics of POAG patients. Results: Forty-three POAG patients and27 controls were completely phenotyped with a full ophthalmologicexamination and static perimetry. Mean age (POAG 67.9 years; controls61.8 years) and sex (POAG 26 males/17 females; controls 11/16) weresimilar 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 thisdifference was statistically significant (p≤0.021). OPA1expression differed between the groups (p≤0.037), but HBBexpression did not differ (p≤0.24). OPA1/HBB was not correlatedwith any clinical feature of POAG patients. Conclusions: Transcriptional analysis ofperipheral blood leucocytes is a limited model system for studying theconsequences of mitochondrial abnormalities in the optic nerve.Nevertheless, OPA1 is known to affect mitochondrial stabilityand has now been implicated in several spontaneous optic neuropathies.Decreased OPA1 expression in POAG patients is anotherindication that mitochondrial function, and possiblymitochondrially-induced apoptosis, may play a role in the developmentof POAG.

[学科分类] 生物化学/生物物理