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Immune Responses in the Glaucomatous Retina: Regulation and Dynamics
Journal article   Open access   Peer reviewed

Immune Responses in the Glaucomatous Retina: Regulation and Dynamics

Valery I. Shestopalov, Markus Spurlock, Oliver W. Gramlich and Markus H. Kuehn
Cells (Basel, Switzerland), Vol.10(1973), p.1973
08/01/2021
DOI: 10.3390/cells10081973
PMCID: PMC8391899
PMID: 34440742
url
https://doi.org/10.3390/cells10081973View
Published (Version of record) Open Access

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.
adaptive immune response dysfunction glaucoma inflammasome innate immune response

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