TY - JOUR
T1 - Immune responses in the glaucomatous retina
T2 - Regulation and dynamics
AU - Shestopalov, Valery I.
AU - Spurlock, Markus
AU - Gramlich, Oliver W.
AU - Kuehn, Markus H.
N1 - Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/8
Y1 - 2021/8
N2 - 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.
AB - 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.
KW - Adaptive immune response
KW - Dysfunction
KW - Glaucoma
KW - Inflammasome
KW - Innate immune response
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U2 - 10.3390/cells10081973
DO - 10.3390/cells10081973
M3 - Review article
C2 - 34440742
AN - SCOPUS:85115192383
VL - 10
JO - Cells
JF - Cells
SN - 2073-4409
IS - 8
M1 - 1973
ER -