Glaucoma

Abstract

Glaucoma is a chronic neurodegenerative disease of the optic nerve, in which apoptosis of retinal ganglion cells (RGCs) and progressive loss of optic nerve axons result in structural and functional deficits in glaucoma patients. This neurodegenerative disease is indeed a leading cause of blindness in the world. The glaucomatous neurodegenerative environment has been associated with the activation of multiple pathogenic mechanisms for RGC death and axon degeneration. Growing evidence obtained from clinical and experimental studies over the last decade also strongly suggests the involvement of the immune system in this neurodegenerative process. Paradoxically, the roles of the immune system in glaucoma have been described as either neuroprotective or neurodestructive. A balance between beneficial immunity and harmful autoimmune neurodegeneration may ultimately determine the fate of RGCs in response to various stressors in glaucomatous eyes. Based on clinical data in humans, it has been proposed that one form of glaucoma may be an autoimmune neuropathy, in which an individual's immune response facilitates a somatic and/or axonal degeneration of RGCs by the very system which normally serves to protect it against tissue stress.

Neuroprotective Agents in Glaucoma

“…Serum and tissue findings, including chronic activation of resident immunoregulatory glial cells, altered T-cell repertoires, increased autoantibody production, retinal immunoglobulin deposition, and complement activation, support the hypothesis that both innate and adaptive immune activity accompany glaucomatous neurodegeneration (Tezel & Wax, 2007). Regarding T-cell cytotoxicity to RGCs, there is in vitro evidence that activated T cells may be directly cytotoxic to RGCs and induce RGC apoptosis mainly through death receptormediated signaling.…”

“…Increased expression of HSPs28 and ROS-dependent controlling pathways seem to be critical for the initiation of an activated immune response (Tezel et al, , 2005. In addition to T-cell-mediated injury, autoantibody-mediated retinal damage has been associated with the pathogenesis of retinal diseases (Khan et al, 2006) .Increased serum autoantibodies to various retina and optic nerve proteins have also been identified in patients with glaucoma over the past decade (Grus et al, 2008;Tezel & Wax, 2007) and retinal immunoglobulin deposition was seen in glaucomatous human donor eyes.There is evidence supporting the hypothesis that exogenously applied antibodies, including HSP antibodies, which exhibit increased serum titers in many patients with glaucoma, can be internalized by retinal neurons. At concentrations similar to those found in the patient serum, these antibodies can facilitate neuronal apoptosis (Tezel and Wax, 2000b) .…”

Expression of Matrix Metalloproteinases in Lacrimal Fluid and Gene Polymorphism of Complement Factor H (Cfh) in Patients With Primary Open-Angle Glaucoma

“…Клинические и экспериментальные исследования последних лет подтвердили участие иммунной системы в нейродегенеративных реакциях, развивающихся в сетчатке и зрительном нерве, а также в более высоких отделах зрительного тракта при ПОУГ [6,13,30]. Активизация аутоиммунитета при глау-коме доказана работами Tezel G. (2007; [31,33], Wax M.B. (2009) [35], Курышевой Н.И.…”

Stem cell sources and therapeutic approaches for central nervous system and neural retinal disorders

“…One major advantage of the inner retina and optic nerve is that molecularly the mechanisms that ultimately result in RGC apoptosis and optic nerve loss are the same classic mechanisms described for neurodegenerative events in other parts of the CNS. 28,98,152 As such, both basic and clinical stem cell therapy investigations that target the inner retina and optic nerve might provide results that translate to or, at least guide, further research into similar therapies for other neurodegenerative disorders.…”