Predictive role of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in normal-tension glaucoma.

As a type of primary open-angle glaucoma, normal-tension glaucoma (NTG) is a health problem that manifests itself with low intraocular pressure (IOP) levels and preserves its importance for public health care. In population-based screenings, which take the IOP levels of 21mmHg as a cut-off for the diagnosis of glaucoma, the diagnosis is usually delayed, and the treatment is started in an advanced stage by the referred ophthalmologists. NTG is associated with some autoimmune conditions and systemic diseases, such as paraproteinemia, nocturnal hypotension, and migraine. Recently, a simple and cheap test (namely the hemogram) was defined as measure of systemic inflammation, measuring the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). A recent study displayed an altered platelet function in NTG patients. We hypothesize that an automated hemogram analysis for NLR together with IOP measurements may be used to screen NTG patients who are admitted to primary care clinics if any relationship between NTG and NLR could be demonstrated in future researches.

Human TBK1: A Gatekeeper of Neuroinflammation.

The importance of TANK binding kinase-1 (TBK1), a multimeric kinase that modulates inflammation and autophagy, in human health has been highlighted for the first time by the recent discoveries of mutations in TBK1 that underlie amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), normal tension glaucoma (NTG) or childhood herpes simplex encephalitis (HSE). Gain-of-function of TBK1 are associated with NTG, whereas loss-of-function mutations result in ALS/FTD or in HSE. In light of these new findings, we review the role of TBK1 in these seemingly unrelated, yet allelic diseases, and discuss the role of TBK1 in neuroinflammatory diseases. This discovery has the potential to significantly increase our understanding of the molecular basis of these poorly understood diseases.

Selected autoantibodies and normal-tension glaucoma.

BACKGROUND: Although intraocular pressure is an important risk factor in glaucoma, there is growing body evidence indicating an immunological component in the pathogenesis of normal-tension glaucoma (NTG). The aim of this study was to determine if NTG coexists with elevated levels of autoantibodies detected in rheumatic diseases. MATERIAL AND METHODS: We enrolled 105 patients into the study: 35 with NTG, 34 with primary open-angle glaucoma (POAG), and 36 controls. All patients underwent ophthalmic examination and blood tests. Blood was examined for the level of: antibodies against antinuclear antibodies (ANA), antibodies to extractable nuclear antigens (ENA), immunoglobulins (IgG, IgA, IgM), rheumatoid factor, anti-citrullinated protein antibodies (ACPA), and antiphospholipid antibodies (anticardiolipin antibodies, beta2-glycoprotein I antibodies, antiprothrombin antibodies). RESULTS: The level of ANA was increased among 6 patients in the NTG group (17.1%), 8 in the POAG group (23.5%), and 6 in the control group (16.5%). The difference was not statistically significant (p=0.97). None of the patients in the NTG, POAG, or control group had positive antibodies to ENA. The level of immunoglobulins IgG, IgM, and IgA in the 3 groups was similar and within normal values. The median level of rheumatoid factor and ACPA was the highest in the NTG group, but it was within normal laboratory values. There was a statistically significant difference between antiprothrombin antibodies IgG between the NTG and POAG group (p=0.01), but not between the NTG and control group (p=0.24). CONCLUSIONS: The results of our study do not confirm the hypothesis that NTG coexists with elevated blood levels of antibodies, which are a characteristic feature of rheumatic diseases.

Investigation of the association between Helicobacter pylori infection and normal tension glaucoma.

PURPOSE: To investigate whether Helicobacter pylori infection is associated with normal tension glaucoma (NTG). METHODS: One hundred consecutive NTG patients (group 1) from an outpatient glaucoma clinic were enrolled. Medical records of the 88 control participants (control 1) of the outpatient clinic, and 104 NTG patients (group 2) and 1116 healthy controls (control 2) (1220 subjects in total) from a primary health care center were reviewed retrospectively to compare the results. Serum samples from all subjects were analyzed for the presence of H. pylori-specific immunoglobulin G antibodies using ELISA. The distributions of serologic H. pylori test results of the NTG patients and control subjects were compared, and possible associations between clinical phenotypes and positive serologic results were assessed. Bilaterality of NTG patients was also analyzed. RESULTS: NTG patients had significantly more positive serologic results than did the healthy controls. There were significant differences between group 1 and control 1 patients (P = 0.020; odds ratio [OR], 2.05), group 1 and control 2 patients (P = 0.016; OR, 1.73), and group 2 and control 2 patients (P = 0.008; OR, 1.83). However, no significant association was found between clinical characteristics and a positive serologic result for H. pylori in NTG patients. CONCLUSIONS: This study suggests that H. pylori infection may be associated with an increased risk for NTG. H. pylori may play a role in the development or progression of NTG as a secondary aggravating factor because of the coexistence of other main causes or it may be the primary cause.

Valosin-containing protein is a novel autoantigen in patients with glaucoma.

PURPOSE: The purpose of this study was to identify novel autoantigens that react with specific serum autoantibodies in patients with glaucoma. METHODS: Sera from patients with glaucoma (n = 80) and healthy subjects without a known pathology (n = 20) were investigated by immunoblot performed with bovine optic nerve lysates and resolved by one- and two-dimensional electrophoresis. Proteins in the immunoreactive spots were selected and identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) data analysis. All the sera from subjects were assayed using enzyme-linked immunosorbent assay to identify autoantibodies. RESULTS: We selected two prominent bands with molecular weights of 100 and 220 kDa by 8% sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis, and these two bands were only found in the glaucoma patients. Using one-dimensional electrophoresis and LC-MS/MS analyses, we identified these proteins to be valosin-containing protein (VCP) and fodrin, respectively, and using two-dimensional electrophoresis and LC-MS/MS analyses, VCP was identified to be a common target antigen. In patients with primary open angle glaucoma and normal tension glaucoma, the frequency of autoantibodies to recombinant human VCP was 42.0 and 23.3%, respectively (p < 0.002). In the enzyme-linked immunosorbent assay tests, autoantibody titers to recombinant human VCP were significantly higher than that in healthy controls (p < 0.025). CONCLUSIONS: VCP represents a potential candidate target for autoantibodies on the optic nerve in patients with glaucoma.

[Relationship between oxidatve stress and autoimmunity in glaucoma]. / Zusammenhang zwischen oxidativem Stress und immunologischen Störungen beim Glaukom.

Elevated intraocular pressure does not explain glaucoma in all patients, but there is information that autoimmune mechanisms may be involved in this disorder. We have demonstrated in several studies that glaucoma patients reveal changes in their immune reactivities against ocular antigens. The mechanisms of these reactivities are still widely unknown, but oxidative pathways could play a major role. There is evidence that free radicals are able to alter the ability of glial cells to be recognized as antigens. Furthermore, one can assume that during the aging process posttranslational changes, e. g., oxidation of ocular antigens increase with age. It is feasible that these changed antigens may trigger such changes. in an autoimmune glaucoma animal model we have shown that immunological processes after immunisation can lead to a loss of retinal ganglion cells. Considering that these changes in natural autoimmunity can be found consistently amongst different study populations, it might be a promising new tool for glaucoma diagnosis and new therapeutic immunomodulating options.