Abstract
Pyroptosis is a lytic form of programmed cell death mediated by gasdermins (GSDMs) with pore-forming activity in response to certain exogenous and endogenous stimuli. The inflammasomes are intracellular multiprotein complexes consisting of pattern recognition receptors, an adaptor protein ASC (apoptosis speck-like protein), and caspase-1 and cause autocatalytic activation of caspase-1, which cleaves gasdermin D (GSDMD), inducing pyroptosis accompanied by cytokine release. In recent years, the pathogenic roles of inflammasomes and pyroptosis in multiple eye diseases, including keratitis, dry eyes, cataracts, glaucoma, uveitis, age-related macular degeneration, and diabetic retinopathy, have been continuously confirmed. Inhibiting inflammasome activation and abnormal pyroptosis in eyes generally attenuates inflammation and benefits prognosis. Therefore, insight into the pathogenesis underlying pyroptosis and inflammasome development in various types of eye diseases may provide new therapeutic strategies for ocular disorders. Inhibitors of pyroptosis, such as NLRP3, caspase-1, and GSDMD inhibitors, have been proven to be effective in many eye diseases. The purpose of this article is to illuminate the mechanism underlying inflammasome activation and pyroptosis and emphasize its crucial role in various ocular disorders. In addition, we review the application of pyroptosis modulators in eye diseases.
Highlights
Pyroptosis, a programmed cell death dependent on the pore-forming activity of the gasdermin protein family with an inflammatory response, plays an essential part of the body’s intrinsic immune response in antagonizing pathogen infection and sensing endogenous risk signals (Man et al, 2017; Shi et al, 2017)
We summarize the mechanisms and functions of pyroptosis and inflammasomes in various ocular disorders
Our current knowledge of pyroptosis occurring in eye disease is just the tip of the iceberg
Summary
Pyroptosis, a programmed cell death dependent on the pore-forming activity of the gasdermin protein family with an inflammatory response, plays an essential part of the body’s intrinsic immune response in antagonizing pathogen infection and sensing endogenous risk signals (Man et al, 2017; Shi et al, 2017). The first programmed cell death to be described, can be initiated through extrinsic and intrinsic pathways and characterized by cell contraction, nuclear condensation and division, and dynamic membrane blistering and loss. It activates the execution phase of cell death and allows the clearance of apoptotic cells without eliciting an inflammatory response, which is critical to physiological homeostasis in almost every organ system (Galluzzi et al, 2018). The goal of this review is to discuss the role of pyroptosis and inflammasomes in the pathogenesis of ocular disorders and the application of pyroptosis inhibitors in eye diseases
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