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Neuroinflammation and microglia in glaucoma: time for a paradigm shift
Author(s) -
Wei Xin,
Cho KinSang,
Thee Eric F.,
Jager Martine J.,
Chen Dong Feng
Publication year - 2019
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.24256
Subject(s) - glaucoma , neuroinflammation , optic nerve , medicine , microglia , neuroscience , retinal ganglion cell , intraocular pressure , normal tension glaucoma , ophthalmology , inflammation , immunology , biology , open angle glaucoma
Glaucoma is a complex neurodegenerative disease with many clinical subtypes. Some of its rare forms include pigmentary glaucoma, uveitic glaucoma and congenital glaucoma. While they all share common features of progressive retinal ganglion cell (RGC) loss, optic nerve damage and corresponding visual field loss, the exact mechanisms underlying glaucomatous neuron loss are not clear. This has largely hindered the development of a real cure for this disease. Elevated intraocular pressure (IOP) is a known major risk factor of glaucoma; however, progressive degeneration of RGCs and axons can also be found in patients with a normal IOP, i.e., normal tension glaucoma (NTG). Interestingly, patients who carry the gain‐of‐function mutation of the pro‐inflammatory gene TBK1 – tumor necrosis factor (TNF) receptor associated factor NF‐κB activator (TANK) binding kinase 1 – are at increased risk to develop NTG. This finding suggests a causal link between neuroinflammatory processes and glaucoma. Various studies have reported the presence of neuroinflammatory responses by microglia, astrocytes and other blood‐born immune cells in the optic nerve head (ONH) at early stages of experimental glaucoma. Inhibition of certain pro‐inflammatory pathways, particularly those associated with microglial activation, appears to be neuroprotective. In this review, we will focus on the inflammatory responses, in particular the proposed roles of microglia, in the pathogenesis of glaucoma.