Immune Responses in the Glaucomatous Retina: Regulation and Dynamics

Cells

Markus Spurlock¹  Valery I. Shestopalov²  Markus H. Kuehn³  Oliver W. Gramlich³ 

[1] Department of Cell and Developmental Biology, Miller School of Medicine, University of Miami, Miami, FL 33101, USA;Department of Ophthalmology, Miller School of Medicine, University of Miami, Miami, FL 33101, USA;Department of Veterans Affairs, Center for the Prevention and Treatment of Visual Loss, Iowa City, IA 52246, USA;

关键词: glaucoma;    innate immune response;    dysfunction;    inflammasome;    adaptive immune response;   

DOI  :  10.3390/cells10081973

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown