Bosley Thomas M, Hellani Ali, Spaeth George L, Myers Jonathan, Katz L Jay, Moster Marlene R, Milcarek Barry, Abu-Amero Khaled K
Ophthalmic Genetics Laboratory and Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
Mol Vis. 2011 Apr 27;17:1074-9.
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.
Patients were eligible for inclusion if they met standard clinical criteria for POAG, including age greater than 40 years, intraocular pressure ≥ 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 β-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.
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≤0.021). OPA1 expression differed between the groups (p≤0.037), but HBB expression did not differ (p≤0.24). OPA1/HBB was not correlated with any clinical feature of POAG patients.
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.
杂合性1型视神经萎缩（OPA1）突变是显性视神经萎缩的病因，而在Leber遗传性视神经病变患者中OPA1表达下调可能意味着线粒体中的Opa1蛋白水平在其他自发性视神经病变中也起作用。线粒体和代谢异常可能使原发性开角型青光眼（POAG）患者的视神经面临风险，本初步研究旨在调查在POAG的进行性视神经病变中是否存在OPA1表达改变。
符合POAG标准临床标准的患者纳入研究，标准包括年龄大于40岁、治疗前至少一只眼眼压≥21 mmHg、房角镜检查双侧前房角外观正常以及具有POAG特征性的视神经损伤。从白细胞中提取RNA，通过逆转录酶转化为cDNA，并使用实时PCR评估OPA1和β-球蛋白（HBB）管家基因的表达水平。将POAG患者的OPA1表达与HBB表达之比（OPA1/HBB）与对照组进行比较，并与POAG患者的临床特征进行比较。
43例POAG患者和27例对照者进行了全面的眼科检查和静态视野检查以完成表型分析。两组的平均年龄（POAG组67.9岁；对照组61.8岁）和性别（POAG组26例男性/17例女性；对照组11例/16例）相似。POAG患者的平均OPA1/HBB（1.16，标准差0.26）比对照组（1.41，标准差0.50）低18%，且差异具有统计学意义（p≤0.021）。两组间OPA1表达存在差异（p≤0.037），但HBB表达无差异（p≤0.24）。OPA1/HBB与POAG患者的任何临床特征均无相关性。
外周血白细胞的转录分析是研究视神经线粒体异常后果的有限模型系统。然而，已知OPA1会影响线粒体稳定性，现已发现其与多种自发性视神经病变有关。POAG患者中OPA1表达降低是线粒体功能以及可能的线粒体诱导凋亡在POAG发病中起作用的又一证据。
