Glial cell interactions and glaucoma

Abstract

Purpose of reviewThe present review describes new advances in our understanding of the role of glial cells in the pathogenesis of glaucoma. It is becoming clear that retinal glia should not be studied in isolation in glaucoma because glia have dynamic and diverse interactions with a range of different cell types that could influence the disease process.Recent findingsMicroglial activity is modulated by signals from retinal ganglion cells and macroglia that influence RGC survival in various models of injury. New studies suggest that circulating monocytic populations may play a role in mediating the immune response to glaucoma. Astrocytes have been found to develop discrete localized processes that interact with a specific subset of retinal ganglion cells, possibly responding to the expression of phagocytic signals by stressed retinal ganglion cells.SummaryRetinal glia constitute a highly versatile population that interacts with various cells to maintain homeostasis and limit disease. Defining the mechanisms that underlie glial communication could enable the development of more selective therapeutic targets, with great potential clinical applications.

siRNA-Mediated Knockdown of the mTOR Inhibitor RTP801 Promotes Retinal Ganglion Cell Survival and Axon Elongation by Direct and Indirect Mechanisms

“…In glaucoma, for example, activated microglial-derived proinflammatory factors, such as TNF-a and IL-6, may induce neurotoxicity rather than neuroprotection. 79 Time-course analyses of gene expression changes during reactive gliosis found more than 1300 genes differentially expressed within 1 day of ONC, with functionally distinct groups of temporally specific genes associated with inflammatory responses, tissue remodeling, and structural alterations. 80 Modulation of retinal gliosis to optimize RGC survival and axon regeneration must therefore consider multiple tissue-specific, injury-specific, and temporal factors.…”

Evidence Supporting an Association Between Expression of Major Histocompatibility Complex II by Microglia and Optic Nerve Degeneration During Experimental Glaucoma

“…38 The precise method by which minocycline protects RGCs, and, by implication, the specific mechanism(s) by which the microglia are toxic to RGCs, remain unclear, but suggested pathways of microglial toxicity include release of proinflammatory mediators and activation of the immune system. 3,6,7 In this context, it is noteworthy that minocycline has been shown to downregulate MHC II RT1B expression within spinal cord microglia and macrophages and concurrently reduce the severity of EAE symptoms. 39 MHC II molecules expressed by activated microglia present antigenic fragments to the immune system for recognition and activation of CD4 + T cells.…”

“…[1][2][3][4] Microglia serve as the resident immune cells of the CNS, constantly surveying the environment and responding rapidly to disruption of local tissue homeostasis. Neuronal damage triggers microglia to adopt a reactive phenotype that encompasses multiple changes including proliferation, migration, phagocytosis of dying neurons, stimulation of neuroinflammatory pathways, and antigen presentation.…”

“…Neuronal damage triggers microglia to adopt a reactive phenotype that encompasses multiple changes including proliferation, migration, phagocytosis of dying neurons, stimulation of neuroinflammatory pathways, and antigen presentation. 3,5 It has indisputably been proven that microglia within the retina and optic nerve (ON) become reactive in response to RGC degeneration in animal models of glaucoma. 3,6,7 Of arguably greater interest, however, is the recent finding that alterations in microglial function may, in fact, precede RGC injury in glaucoma.…”

“…3,5 It has indisputably been proven that microglia within the retina and optic nerve (ON) become reactive in response to RGC degeneration in animal models of glaucoma. 3,6,7 Of arguably greater interest, however, is the recent finding that alterations in microglial function may, in fact, precede RGC injury in glaucoma. 8,9 This result further focuses debate on whether microglial activation is detrimental or beneficial to RGC survival.…”