The role of immune reactions in the pathogenesis of optic neuropathy in normal tension glaucoma

PURPOSE: To analyze molecular and immunological mechanisms of optic neuropathy development in patients with normal tension glaucoma. METHODS: We have been studying serologic indicators of autoantibodies (AB) in patients with normal tension glaucoma (NTG, n=31), which were compared to corresponding parameters in patients with primary open-angle glaucoma (POAG, n=30). The control group consisted of 25 somatically healthy individuals without ophthalmic pathology and clinical symptoms of systemic autoimmune diseases. For the immunological part of the research we used a wide range of antigens: ENO-1, MBP, NSE, Tβ4, α-crystallin, rhodopsin, GAPDH, actin, α-fodrin. The antibody formation in blood serum was determined with the use of the enzyme-linked immunosorbent assay (ELISA). Antibodies concentration in the blood serum was reflected in a spectrophotometric indicator measured in standard units of optical density. RESULTS: Systemic immune disorders in patients with both forms of glaucoma were revealed. In the NTG group the level of AB to rhodopsin decreased from 1.13±0.13 (Mean±SD) to 0.91±0.19 (p=0.00002, p <0.001), to α-fodrin - from 0.39±0.17 to 0.26±0.11 (p=0.00107, p <0.01), to ENO1 - from 0.56±0.19 to 0.28±0.09 (p<0.001), to actin - from 0.50±0.21 to 0.36±0.14 (p=0.00428, p <0.01) and NSE - from 0.37±0.08 to 0.29±0.10 (p=0.00201, p<0.01). At the same time AB levels to α-crystallin increased from 0.29±0.16 to 1.14±0.18 (p <0.001). Immune disorders in the POAG group were expressed by: the decrease of AB to ENO1 level from 0.56±0.19 to 0.36±0.14 (p<0.001), Tβ4 - from 0.23±0.11 to 0.16±0.03 (p=0.00205, p<0.01), actin - from 0.50±0.21 to 0.33±0.10 (p=0.00078, p<0.001) and of AB to α-fodrin - from 0.39±0.17 to 0.30±0.09 (p=0.01513, p<0.05). Meanwhile, AB levels increased in response to α-crystallin from 0.29±0.16 to 1.14±0.38 (p<0.001). The most significant differences in autoimmune indicators between NTG and POAG patients consisted in decrease of AB to rhodopsin level (reliability of intergroup distinctions p=0.00085, p<0.001) and the absence of changes in the levels of AB to Tβ4. In the NTG group we observed a more pronounced decrease in AB serologic indicators to ENO-1 (p<0.001), NSE (p=0.00201, p<0.01) and α-fodrin (p=0.00107, p<0.01), and in the POAG group - a more expressed decrease in AB to Tβ4 (p=0.00205, p<0.01) and actin (p<0.001). CONCLUSION: Complex disorders of immune and molecular homeostasis have been revealed in the NTG group. The study revealed a decreased production of AB to actin, α-fodrin, which are responsible for safety of the neuron cells cytoskeleton, AB to NSE and ENO-1, the markers of nerve cell damage, and to MBP - a marker of demyelination. AB to neuron differentiation antigens - ENO-1 and NSE - can be proposed as serologic markers of optic neuropathy immunodiagnostics in patients with NTG and POAG. Basic distinctions in targets of autoimmune aggression are found in patients with different forms of glaucoma: photoreceptor cells of the retina serve as a target of apoptosis in the NTG group, while in the POAG group the main target is represented by the retinal ganglion cells. Presumably, the target choice for autoimmune aggression in different forms of glaucoma is determined by the nature of the hemodynamic disorders that cause ischemia of either inner or outer layers of the retina.

нормотензивная глаукома, оптическая нейропатия, аутоиммунитет, сывороточные антитела, апоптоз, normal tension glaucoma, optic neuropathy, autoimmunity, serum antibodies, apoptosis

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