Abstract
Glaucoma is a multifactorial disease resulting in progressive vision loss due to retinal ganglion cell (RGC) dysfunction and death. Early events in the pathobiology of the disease include oxidative, metabolic, or mechanical stress that acts upon RGC, causing these to rapidly release danger signals, including extracellular ATP, resulting in micro- and macroglial activation and neuroinflammation. Danger signaling also leads to the formation of inflammasomes in the retina that enable maturation of proinflammatory cytokines such IL-1β and IL-18. Chronic neuroinflammation can have directly damaging effects on RGC, but it also creates a proinflammatory environment and compromises the immune privilege of the retina. In particular, continuous synthesis of proinflammatory mediators such as TNFα, IL-1β, and anaphylatoxins weakens the blood–retina barrier and recruits or activates T-cells. Recent data have demonstrated that adaptive immune responses strongly exacerbate RGC loss in animal models of the disease as T-cells appear to target heat shock proteins displayed on the surface of stressed RGC to cause their apoptotic death. It is possible that dysregulation of these immune responses contributes to the continued loss of RGC in some patients.
Highlights
Glaucoma is a progressive optic neuropathy leading to dysfunction and selective loss of retinal ganglion cells (RGCs) and is the underlying cause of blindness in 80 million people [1,2]
The majority of complement proteins in the bloodstream are synthesized in the liver, and it is likely that the membrane attack complex (MAC) components accumulating on RGC are derived from the blood stream and enter the retina as a result of increased permeability of the blood–retina barrier in glaucoma [112,113]
Majority of complement proteinsand in alternative the bloodcomplement pathway in eye tissue significantly contributes to its immune privilege, there is stream are synthesized in the liver, and it is likely that the MAC components accumualso a body of evidence demonstrating the presence of regulatory complement compounds lating on RGC are derived from the blood stream and enter the retina as a result of insuch as permeability
Summary
Glaucoma is a progressive optic neuropathy leading to dysfunction and selective loss of retinal ganglion cells (RGCs) and is the underlying cause of blindness in 80 million people [1,2]. Data from a number of studies have indicated that patients with higher mean deviation at standard automated perimetry at the onset of the trial are less likely to respond to treatment and are more likely to continue to exhibit vision loss than those with a lower mean deviation [14,15] It appears that maximum IOP is often more predictive of future vision loss than average IOP, suggesting that an initiating event can predispose to subsequent damage [16]. We will focus on the factors contributing to the innate immune responses occurring in the retina early in glaucoma and how these could lead to adaptive immune responses during later stages of the disease These events have been divided into early, intermediate, and late events. Within a specific retinal region, late events will not occur unless early and intermediate events have taken place
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