Autoantibody against neuron-specific enolase found in glaucoma patients causes retinal dysfunction in vivo.
OBJECTIVE
In our recent paper, we have reported the presence of serum autoantibody against neuron-specific enolase (NSE) in patients with glaucoma. The purpose of the present study was to investigate further the pathological effects of anti-NSE antibody on retina by comparing them with the effects induced by N-methyl-D-aspartate (NMDA).


METHODS
Either a glaucoma patient's serum or purified anti-NSE antibody, or 10-40 mM NMDA was intravitreously administered into Lewis rat eyes, and electrophysiological, histopathological, and biochemical evaluations were performed. In addition, the neuroprotective effects of anti-glaucoma drugs, such as timolol, betaxolol, nipradilol, and isopropyl unoprostone, and a calcium antagonist were also studied using these animal models.


RESULTS
Electron microscopy revealed that intravitreal administration of a glaucoma patient's serum, which immunoreacted with retinal 50 kDa 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 electroretinogram (ERG) responses and a remarkable decrease in rhodopsin phosphorylation reaction. These changes were comparable to the effects observed after the intravitreal administration of 20 mM NMDA. Co-administration of nipradilol, an alpha- and beta-blocker, with anti-NSE antibody or 20 mM NMDA caused marked recovery of the affected ERG responses within 2 weeks. In contrast, administration of timolol or betaxolol showed no recovery effect on the ERG responses. Among these drugs, only betaxolol showed a recovery effect on NMDA-induced decrease of rhodopsin phosphorylation. Nilvadipine functioned beneficially on both impaired ERG and rhodopsin phosphorylation reactions observed in rat eyes injected intravitreously with anti-NSE antibody or NMDA. These effects of nilvadipine were not changed by the addition of endothelin-1. In contrast, isopropyl unoprostone had no effect on these functions.


CONCLUSIONS
These observations suggest that serum autoantibody against NSE found in some patients with glaucoma induces retinal dysfunction in vivo, similarly to NMDA.
Maruyama
Ikuyo
I
Department of Ophthalmology, Hirosaki University School of Medicine, Aomori Prefecture, Hirosaki, Japan.
Maeda
Tadao
T
Okisaka
Shigekuni
S
Mizukawa
Atsushi
A
Nakazawa
Mitsuru
M
Ohguro
Hiroshi
H
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000368:Aged; D000818:Animals; D000937:Antigen-Antibody Reactions / Q000276:immunology; D000959:Antihypertensive Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001323:Autoantibodies / Q000494:pharmacology*; D001324:Autoantigens / Q000276:immunology*; D015153:Blotting, Western; D004596:Electroretinography; D005260:Female; D005902:Glaucoma, Open-Angle / Q000276:immunology*; D006801:Humans; D016202:N-Methylaspartate / Q000494:pharmacology; D010751:Phosphopyruvate Hydratase / Q000276:immunology*; D010766:Phosphorylation; D051381:Rats; D011917:Rats, Inbred Lew; D012164:Retinal Diseases / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D012243:Rhodopsin / Q000378:metabolism
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D000959:Antihypertensive Agents; D001323:Autoantibodies; D001324:Autoantigens; D016202:N-Methylaspartate; D012243:Rhodopsin; D010751:Phosphopyruvate Hydratase