Increased VE-822 intraocular pressure is considered a major risk factor, although numerous studies have suggested that WY 14643 Glaucomatous neuropathy actually involves multiple factors, including impaired intraocular blood circulation, excitotoxic reactions caused by excess accumulation of glutamate, free radical production and oxidative stress, increased NO levels, and immunological factors. The role of immunological factors in glaucoma has always been a major research topic. Becker et al. first discovered plasma cells and immunoglobulins in trabecular biopsies of glaucomatous eyes, suggesting changes in humoral immunity. Later, a series of studies reported abnormalities in serum cytokines, antibodies, and the complement system. For example, higher levels of antibodies against small heat shock proteins were found in normal tension glaucoma patients, and several autoantibodies such as HSP70, anti-phosphatidylserine, ��-enolase, glycosaminoglycans, vimentin and retinal S-antigen were identified in glaucoma. What��s more, the advances and understanding made in both animal models of glaucoma as well as in human glaucoma autopsy findings in the 90��s and 00��s suggests there is a fundamental role of the immune system in mediating neuronal cell death in glaucoma regardless of intraocular pressure. Cytokines mediate immune and inflammatory responses in many situations and are widely involved in the process of glaucomatous optic neuropathy. T-helper cells are the main source of cytokines and can be classified into subsets by their cytokine production profiles. Th1 cells play a critical role in the regulation of cellular immunity by secreting interferon- gamma, interleukin -2, IL-12, and tumor necrosis factor -��. Th2 cells regulate humoral immunity by producing IL-4, IL-5, IL-6, IL-10, and IL-13. The concept of imbalanced Th subsets has been associated with a number of infectious and autoimmune diseases, allergies, immunodeficiencies, tumor progression, failed pregnancy, and graft rejection. The concept of immune balance has recently been introduced to the study of central nervous system disorders. A variety of cell types in the central nervous system produce and secrete cytokines, including neurons, microglia cells, stellate cells, and endothelial cells. Astrocytes and microglial cells play roles similar to those of Th1 and Th2 cells, respectively. Glaucomatous optic neuropathy is a degenerative disease of the nervous system. Our previous clinical study showed significantly lower serum TNF-�� in primary open-angle glaucoma patients than in controls, while the levels of IL-4, IL-6, and IL-12p70 were significantly higher.