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

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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