Elsevier

Japanese Journal of Ophthalmology

Volume 46, Issue 1, January–February 2002, Pages 13-17
Japanese Journal of Ophthalmology

Laboratory investigation
Clinical Significance of Serum Antibody Against Neuron-Specific Enolase in Glaucoma Patients

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Abstract

Purpose: In a recent study, we found the presence of serum autoantibody against neuron-specific enolase (NSE) in glaucoma patients. The purpose of the present paper is to investigate further the clinical significance of the presence of the serum antibody against NSE in glaucoma patients.

Methods: Serum autoantibody against NSE was examined by Western blot analysis in 143 patients with glaucoma (normal tension glaucoma [NTG], 45 cases; primary open angle glaucoma [POAG] 98 cases). Clinical characteristics including visual acuity, visual field, intraocular pressure (IOP), and optic disc features were compared between the serum autoantibody-positive and the serum autoantibody-negative patients.

Results: Maximum IOP in the serum anti-NSE antibody-positive patients was significantly lower than that in the negative patients (P < .05). However, no statistical differences were observed in visual field loss, disc cupping, or other clinical factors. During the clinical course, rates of the presence of anti-NSE antibody were significantly higher in the early stages of POAG (P < .0001) with visual field deterioration than without it. Although it was not statistically significant, the positive rates of serum anti-NSE antibody were relatively higher in the later stages of POAG and NTG with visual field deterioration than without it.

Conclusion: The present observations suggest that the presence of serum autoantibody against NSE may be clinically useful for predicting the progression of visual field loss in POAG patients.

Introduction

Glaucomatous optic neuropathy is characterized by loss of retinal ganglion cells and their axons, excavated appearance of the optic nerve head, and progressive loss of visual field sensitivities.1 In terms of its pathology, apoptotic cell death of retinal ganglion cells is known to be involved, based upon postmortem studies of human eyes with primary open-angle glaucoma (POAG)2 or neovascular glaucoma,3 and experimental glaucoma models with elevated intraocular pressure (IOP).4, 5 As the molecular mechanism triggering the apoptosis, deprivation of neurotrophic factors,4 ischemia,6 chronic elevation of glutamate,7 and disorganized nitric oxide (NO) metabolism8 have been implicated. In addition it was reported that autoimmune responses toward rhodopsin,9 60-kDa heat shock protein (hsp 60),10 27-kDa heat shock protein (hsp 27), and α-crystallin11 may be related to the apoptotic cell death process in some glaucoma patients, particularly in those patients with normal tension glaucoma (NTG). Recently, we have found that approximately 20% of POAG patients possessed serum antibody against neuron-specific enolase (NSE), and that maximum IOP levels in POAG patients with anti-NSE antibody were statistically lower than in POAG patients without the antibody. However, other clinical factors, including visual field defects, medication, and optic nerve cupping, were comparable between the antibody-positive and -negative POAG patients.12 In addition, injection of the patient's serum into the vitreous cavity of a Lewis rat caused reduction in the b-wave in electroretinography (ERG) and TdT-dUTP terminal nick-end labeling (TUNEL)-positive staining within the retinal ganglion cells, and these effects were comparable to those caused by the excitotoxicity induced by N-methyl-D-aspartate (NMDA). Therefore, based upon these findings we suggested that serum anti-NSE antibody may be one of the clinical factors responsible for deteriorating glaucomatous optic neuropathy. A rat model intravitreously injected with the anti-NSE antibody has proved to be useful for understanding the molecular pathology of glaucoma and the evaluation of several anti-glaucoma drugs.

Here, to study further the clinical significance of the presence of the anti-NSE antibody in glaucoma patients, we have performed a clinical characterization of a greater number of glaucoma patients.

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Materials and Methods

The studies were performed in accordance with the guidelines set by Hirosaki University and the Declaration of Helsinki on Biomedical Research Involving Human Subjects. The protocols were approved by the institution's Committee for the Protection of Human Subjects.

Results

As shown in Table 1, serum antibody against NSE was recognized in 20% of the glaucoma patients. As we reported previously12 using a small number of patients, (1) in POAG, maximum and mean IOP levels were statistically and relatively lower in the antibody-positive patients than in the -negative patients; and (2) other clinical factors including, visual field defects, medication, and optic nerve cupping, were almost identical between the two groups of POAG and NTG patients. These findings were

Discussion

Elevation of IOP is known to be a major causative factor in the progression of glaucomatous visual field losses.17 However, several clinical investigations have revealed that approximately 20–30% of POAG patients showed progressive deterioration of visual field defects even though the IOP levels were controlled at the lower levels.18 Therefore, this observation suggests that in addition to elevated IOP, some unknown mechanisms must be present causing glaucoma progression. In our previous study,

References (21)

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