Laboratory investigationClinical Significance of Serum Antibody Against Neuron-Specific Enolase in Glaucoma 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,
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Inflammatory and immunological aspects of glaucoma, optic neuritis, and neuromyelitis optica impacting eyesight
2023, Translational Neuroimmunology: Neuroinflammation: Volume 7Autoimmune aspects in glaucoma
2016, European Journal of PharmacologyDoes autoimmunity play a part in the pathogenesis of glaucoma?
2013, Progress in Retinal and Eye ResearchCitation Excerpt :Importantly, we also found differences of autoantibody patterns between POAG and NTG (Grus et al., 2004). Meanwhile, disease-specific changes in complex profiles of naturally occurring IgG autoantibodies could be detected in sera of glaucoma patients (Grus et al., 2004; Joachim et al., 2003, 2005, 2008, 2007b) and several autoantibodies against ocular antigens, such as glycosaminoglycans (Tezel et al., 1999), myelin basic protein (MBP) (Joachim et al., 2008), vimentin (Joachim et al., 2007a), glial fibrillary acidic protein (GFAP) (Joachim et al., 2008), α-fodrin (Grus et al., 2006), γ-enolase (Maruyama et al., 2000), anti-phosphatidylserine (Kremmer et al., 2001), retinaldehyde-binding protein (Reichelt et al., 2008), retinal S-antigen (Reichelt et al., 2008), neuron specific enolase (Ikeda et al., 2002), or glutathione-S-transferase (Yang et al., 2001) have been identified. The enormous complexity of antibodies makes research challenging in this field, but interestingly, we could show that these complex antibody profiles do exist among different study populations and Fig. 2 displays IgG antibody patterns in NTG patients in study populations from Germany and the United States (Grus et al., 2006).
Autoimmune biomarkers in glaucoma patients
2013, Current Opinion in PharmacologyCitation Excerpt :Furthermore, disease-specific changes in complex profiles of naturally occurring IgG autoantibodies were detected in sera of glaucoma patients [6–13] with a high consistency throughout different study populations [14] (Figure 1). Several autoantibodies, such as against, HSP70 [15], anti-phosphatidylserine [16], γ-enolase [17], glycosaminoglycans [18], neuron specific enolase [19], glutathione-S-transferase [20], α-fodrin [14] (Figure 1), vimentin [15], myelin basic protein (MBP) [8], glial fibrillary acidic protein (GFAP), retinaldehyde-binding protein [21], or retinal S-antigen [21] were identified and implicate a role for autoimmunity in glaucoma. However, it still remains unclear if the autoantibodies seen in glaucoma develop during the disease as a consequence, or are causative.
Evaluation of presumptive biomarkers of oxidative stress, immune response and apoptosis in primary open-angle glaucoma
2013, Current Opinion in PharmacologyCitation Excerpt :In fact, Toll-like receptors (TLR) of the innate immune system, recognizing molecules derived from microbes showed differential proteomic analysis expression in glaucomatous human retina [29]. Complex autoantibody repertoires in the serum of POAG populations [30,31–33], and against both the RGC neuron specific enolase (NSE) [31] and retinal, optic nerve, and optic nerve head antigens have also been described in relation to glaucoma progression [34]. Interestingly, it was reported enhanced T-cell activity resulting from immunization against a synthetic copolymer (COP-1) designed to mimic myelin basic protein, neuroprotecting the RGC in animal glaucoma models [35].
Serological Levels of Anti-clathrin Antibodies Are Decreased in Patients With Pseudoexfoliation Glaucoma
2021, Frontiers in Immunology