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）血清自身抗体在青光眼患者中的临床作用及其对视网膜的病理影响。对象和方法：采用western blot和酶联免疫吸附法检测73例正常张紧性青光眼（NTG）和169例原发性开角型青光眼（POAG）患者血清抗NSE自身抗体，并评价抗NSE抗体滴度与临床特征的关系。将青光眼患者血清或纯化的抗nse抗体静脉注入Lewis大鼠眼内，进行电生理、组织病理学和生化评价。此外，我们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%的青光眼患者检测到抗nse抗体。抗nse抗体滴度随视力下降呈规律性下降趋势，POAG组视野丧失加重，NTG组视野丧失无系统性变化。有视野恶化的NTG患者抗nse抗体滴度相对高于无视野恶化的NTG患者。电镜观察发现，经western blot分析，青光眼患者血清与视网膜50kDa产生免疫反应，并纯化抗nse抗体，玻璃体内给药可诱导大鼠视网膜神经节细胞凋亡。功能上，这些眼的ERG反应明显减少，视紫红质磷酸化反应明显减少。尼帕地洛尔或倍他洛尔与抗nse抗体联合使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。尼伐地平对受损的ERG和视紫红质磷酸化反应都有有益的作用。结论：这些观察结果提示血清抗NSE自身抗体可能在临床上用于诊断POAG早期阶段和监测NTG青光眼进展，并且在一些青光眼患者中发现的血清抗NSE自身抗体在体内诱导视网膜功能障碍。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