Neuroinflammation in glaucoma: A new opportunity

Abstract

Mounting evidence suggests neuroinflammation is a key process in glaucoma, yet the precise roles are not known. Understanding these complex processes, which may also be a key in other common neurodegenerations such as Alzheimer’s disease, will lead to targeted therapeutics for a disease that affects as many as 80 million people worldwide. Here, we define neuroinflammation as any immune-relevant response by a variety of cell types including astrocytes, microglia, and peripherally derived cells occurring in the optic nerve head and/or retina. In this review article, we first discuss clinical evidence for neuroinflammation in glaucoma and define neuroinflammation in glaucoma. We then review the inflammatory pathways that have been associated with glaucoma. Finally, we set out key research directions that we believe will greatly advance our understanding of the role of neuroinflammation in glaucoma. This review arose from a discussion of neuroinflammation in glaucoma at the 2015 meeting of the The Lasker/IRRF Initiative for Innovation in Vision Science. This manuscript sets out to summarize one of these sessions; “Inflammation and Glaucomatous Neurodegeneration”, as well as to review the current state of the literature surrounding neuroinflammation in glaucoma.

Visions of Eye Commensals: The Known and the Unknown About How the Microbiome Affects Eye Disease

“…Individuals with elevated IOP may not develop disease, and some patients with normal IOP may still develop disease. It is believed that once disease begins, local inflammatory responses can exacerbate glaucoma; however, systemic infections do not appear to contribute to disease outcome . While overproduction and inadequate drainage of aqueous are well‐known causes of high IOP, certain medications and eye trauma may also be contributors.…”

Insights into the Immune System and Glaucoma

“…Once C1 is activated, C3 convertase is triggered by glial cells, which can amplify RGC damage by recruiting other immune cells like monocytes. 20,47 It is still unknown whether the complement pathway is directly responsible for RGC degeneration.…”

“…Immune dysregulation and immune activation in glaucoma pathogenesis are the focus of many studies in both experimental animal models and in human clinical studies. 14,20,30 …”

“…Immune responses are necessary for proper tissue cleaning, maintenance, and repair. 19,20 It has also been proposed that protective or beneficial autoimmunity may help protect against neurodegeneration in the central nervous system (CNS). 11,[21][22][23][24][25] This concept suggests that the immune system plays a key role in the ability of the CNS, like the optic nerve and retina, to withstand neurodegeneration, by recruiting both innate (resident and blood-borne macrophages) and adaptive (self-antigen specific T-cells) cells that together promote a protective niche and hinder disease progression under a wellcontrolled response.…”

“…15,[46][47][48][49] The complement pathway can be activated in either the optic nerve head or in the inner plexiform layer of the retina. 20 It has been shown that RGCs sense damage or stress and respond by activating C1, which is part of the classical complement pathway. Once C1 is activated, C3 convertase is triggered by glial cells, which can amplify RGC damage by recruiting other immune cells like monocytes.…”