Study of autoimmune mechanisms in molecular pathology of glaucomatous optic neuropathy.

目的：进一步探讨抗神经元特异性烯醇化酶(NSE)自身抗体在青光眼患者中的临床意义及其对视网膜的病理影响。对象和方法：采用免疫印迹分析和酶联免疫吸附试验检测73例正常眼压性青光眼(NTG)和169例原发性开角型青光眼(POAG)患者血清中抗NSE自身抗体，并分析其与临床特征的关系。将青光眼患者血清或纯化的抗NSE抗体分别注入Lewis大鼠眼内，进行电生理、组织病理学和生化检测。此外，还利用这些动物模型研究了抗青光眼药物和钙拮抗剂的神经保护作用。结果：约20%的青光眼患者可识别抗NSE抗体。抗nse抗体效价随d…呈规律性下降。POAG患者的视野损失更严重，而NTG患者则未观察到系统性损害。伴有视野损害的NTG患者的抗NSE抗体滴度相对较高。免疫印迹分析显示，玻璃体内注射与视网膜50 kDa免疫反应的青光眼患者血清和纯化的抗NSE抗体可诱导大鼠视网膜神经节细胞凋亡。在功能上，这些眼睛的ERG反应显著降低，视紫红质磷酸化反应显著降低。尼普拉地洛或倍他索洛尔与抗NSE抗体联合应用分别可显著恢复受影响的ERG反应或恢复视紫红质磷酸化降低的效应。尼伐地平对受损的ERG和视紫红质磷酸化反应均有益处。结论：血清抗NSE自身抗体可用于POAG的早期诊断和监测NTG的青光眼进展，部分青光眼患者体内存在抗NSE自身抗体可导致视网膜功能障碍。较少

Purpose : To evaluate further the clinical roles of serum autoantibody against neuron specific enolase(NSE) in glaucoma patients and its pathilogical effects on retina. Subjects and methods : Serum autoantibody against NSE was examined by western blot analysis and enzyme-linke immunosorbent assay in 73 patients with normal tension galucoma(NTG) and 169 patients with primary open angle glaucoma(POAG), and the relationships between the titers of anti-NSE antibody and clinical characteristics were evaluated. Either a glaucoma patient's serum or purified anti-NSE antibody was intravrtreously administrated into Lewis rat eyes, and electrophysiological, histopathological, and biochemical evaluations were performed. In addition, the neuroprotective effects of anti-glaucoma drugs and a calcium antagonist were studied using these animal models. Results : Anti-NSE antibody was recognized in about 20% of glaucoma patients. The titers of anti-NSE antibody showed a regular decreasing pattern with d … More eteriorating visual field losses in POAG, but no systematic pattern was observed in NTG. The anti-NSE antibody titers were relatively higher in NTG with visual field deterioration than in those without it. Electron microsdopy revealed that intravitreal administration of a glaucoma patient's serum, which immunoreacted with retinal 50kDa in western blot analysis, and purified anti-NSE antibody induced retinal ganglion cell apoptosis in rat eyes. Functionally, these eyes showed a significant decrease in ERG responses and a remarkable decrease in rhodopsin phosphorylation reaction. Co-administration of nipradilol or betaxolol with anti-NSE antibody caused marked recovery of the affected ERG responses or a recovery effect on decreased rhodopsin phosphorylation, respectively. Nilvadipine functioned beneficially on both impaired ERG and rhodopsin phospharylation reactions. Cnnclusions : These observations suggest that serum autoantibody against NSE may be clinically useful for diagnosing early stages of POAG, and for monitoring glaucoma progression of NTG and that serum autoantibody against NSE found in some patients with glaucoma induces retinal dysfunction in vivo. Less