Heat shock protein-derived peptides and autoimmunity in glaucoma

This audio article is from VisualFieldTest.com.Read the full article here: https://visualfieldtest.com/en/heat-shock-protein-derived-peptides-and-autoimmunity-in-glaucomaTest your visual field online: https://visualfieldtest.comSupport the show so new episodes keep coming: https://www.buzzsprout.com/2563091/supportExcerpt:Heat Shock Proteins and Immune Responses in Glaucoma Glaucoma is a leading cause of irreversible vision loss, affecting tens of millions of people worldwide (). Normally, glaucoma is linked to high eye pressure, but many patients – especially those with normal-tension glaucoma – have nerve damage despite normal pressure. This has led researchers to look beyond pressure and investigate the immune system’s role. In particular, eye experts have focused on heat shock proteins (HSPs), which are stress-related proteins that help keep nerve cells alive. Under some conditions these HSPs themselves may become targets of the immune system, contributing to nerve damage (). Evidence suggests that T cells (a type of white blood cell) reacting against HSPs can harm the optic nerve. For example, patient studies have found abnormally high levels of antibodies (proteins made by immune B cells) against HSPs in many glaucoma patients. In fact, multiple studies report that glaucoma patients often have elevated serum autoantibodies to HSP27 and HSP60, two common HSPs () (). In the lab, adding these patient antibodies to retinal cells can trigger cell death (), suggesting they are not just markers but may be damaging. In eye fluid (aqueous humor), glaucoma patients also show unique autoantibody “fingerprints,” including unusually high anti–HSP27 levels compared to healthy controls (). Taken together, these human findings point to an autoimmune tendency against HSPs in glaucoma. Evidence from Animal Models Studies in animals strongly support the idea that HSP-specific immune reactions can cause glaucoma-like damage. In classic experiments, scientists immunized healthy rats with HSP-derived peptides (for example, pieces of HSP27 or HSP60). Remarkably, these rats later developed nerve damage very similar to glaucoma () (). For instance, Wax and colleagues (2008) found that rats given HSP27 or HSP60 peptides lost large numbers of retinal ganglion cells (RGCs) – the neurons that form the optic nerve – and their axons in a pattern that closely mimics human glaucoma (). This damage occurred even though eye pressure stayed normal. Another group confirmed that immunizing rats with an optic-nerve extract (which contains many antigens, including HSPs) similarly caused RGC death and optic nerve thinning (). Importantly, these models also showed earlier immune changes: T cells infiltrated the retina days after immunization, and support cells (microglia) became activated, long before the neurons started dying () (). These animal experiments provide direct proof that an HSP-driven immune response can cause glaucoma-like neurodegeneration. Autoantibody Profiles in Patients Studies of glaucoma patients have found immune “signatures” consistent with HSP involvement. Many patients (especially with normal-tension glaucoma) carry autoantibodies against retina and optic nerve proteins, including HSPs () (). For example, researchers have detected antibodies to HSP27 and HSP60 in the blood of these patients (). In postmortem analyses, donor retinas from glaucoma patients showed antibody binding to HSP27 and HSP60 (). Laboratory tests imply these antibodies could be harmful: when anti-HSP27 antibodies from patients are applied to living retinal cells, the cells undergo apoptosis (self-destruct) (). Even the eye fluid of glaucoma patients contSupport the show