Role of Heat Shock Proteins in Glaucoma

Abstract

Glaucoma, one of the most common causes of blindness worldwide, is a multifactorial neurodegenerative disease characterized by damage of retinal ganglion cells and optic nerve degeneration. However, the exact mechanism leading to glaucoma is still not understood. Evidences suggest an immunological involvement in the pathogenesis. Among other immune responses, altered autoantibody patterns were found in glaucoma patients. Especially elevated antibody levels against heat shock proteins (HSPs), like HSP27 or HSP60, were identified. In an animal model, an immunization with these HSPs induced a pressure-independent retinal ganglion cell degeneration and axon loss, hence mimicking glaucoma-like damage. In addition, development of autoreactive antibodies, as well as a glia and T-cell activation, were described in these animals. Recently, we noted that intravitreal HSP27 injection likewise led to a degeneration of retinal ganglion cells and their axons. Therefore, HSP27 might have a direct damaging effect on retinal cells, and might play a key role in glaucoma.

Innate and Autoimmunity in the Pathogenesis of Inherited Retinal Dystrophy

“…For example, the prevalence of single-nucleotide polymorphisms in the genes coding for complement factor H, complement factor I, as well as many other components of the innate immune system bolster the chances of developing AMD in otherwise normal patients [27,28]. In addition, models of glaucoma have shown the presence of macrophages and T-lymphocytes in the eye along with autoantibodies to proteins of the retina [3,4,29,30]. Models of RP have also shown similar features, including monocytic phagocytosis of both diseased and healthy retinal cells as well as numerous cytokines such as interleukin-1, interleuken-6, vascular endothelial growth factor, and others [4,31,32].…”

Immunological and molecular basics of the primary open angle glaucoma pathomechanism

“…It is suggested that HSP-27, although it plays a protective role in neurodegeneration by binding cytochrome c and preventing apoptosome formation, may have a direct damaging effect on RGCs. The elevation of HSP-27-reactive T cells was reported in glaucoma degeneration [ 44 , 45 ]. Immunization with HSP-27 reinforces the neurodegenerative effect on S100 RGCs [ 14 ].…”

Salient Genetic and Proteomic Pathways in Glaucoma

“…[264] While the exact method of CLAN "tightening" the activity of TM cells is unclear, the TM cells express elevated levels of: laminin, alpha-smooth muscle actin, matrix assembly, actin stress fibers and myosin light-chain phosphorylation all of which are associated with ECM [7,264]. The latter TM factors were linked to increased contractile morphology.…”