NLRP3 inflammasome is a cytosolic multiprotein complex formed in response to exogenous environmental stress and cellular damage. The three major components of the NLRP3 inflammasome are the innate immunoreceptor protein NLRP3, the adapter protein apoptosis-associated speck-like protein containing a C-terminal caspase activation and recruitment domain, and the inflammatory protease enzyme caspase-1. The integrated NLRP3 inflammasome triggers the activation of caspase-1, leading to GSDMD-dependent pyroptosis and facilitating the maturation and release of inflammatory cytokines, namely interleukin (IL)-18 and IL-1β. However, the inflammatory responses mediated by the NLRP3 inflammasome exhibit dual functions in innate immune defense and cellular homeostasis. Aberrant activation of the NLRP3 inflammasome matters in the etiology and pathophysiology of various corneal diseases. Corneal alkali burn can induce pyroptosis, neutrophil infiltration, and corneal angiogenesis via the activation of NLRP3 inflammasome. When various pathogens invade the cornea, NLRP3 inflammasome recognizes pathogen-associated molecular patterns or damage-associated molecular patterns to engage in pro-inflammatory and anti-inflammatory mechanisms. Moreover, chronic inflammation and proinflammatory cascades mediated by the NLRP3 inflammasome contribute to the pathogenesis of diabetic keratopathy. Furthermore, overproduction of reactive oxygen species, mitochondrial dysfunction, and toll-like receptor-mediated activation of nuclear factor kappa B drive the stimulation of NLRP3 inflammasome and participate in the progression of dry eye disease. However, there still exist controversies regarding the regulatory pathways of the NLRP3 inflammasome. In this review, we provide a comprehensive overview of recent advancements in the function of NLRP3 inflammasome in corneal diseases and its regulatory pathways primarily through studies using animal models. Furthermore, we explore prospects for pharmacologically targeting pathways associated with NLRP3.

中文翻译：

---

NLRP3 炎性小体在角膜疾病中的最新进展：临床前见解和治疗意义


NLRP3 炎性小体是一种胞质多蛋白复合物，响应外源性环境应激和细胞损伤而形成。NLRP3 炎性小体的三个主要组分是先天免疫受体蛋白 NLRP3、含有 C 端 caspase 激活和募集结构域的衔接蛋白凋亡相关斑点样蛋白，以及炎性蛋白酶 caspase-1。整合的 NLRP3 炎性小体触发 caspase-1 的激活，导致 GSDMD 依赖性焦亡，并促进炎性细胞因子（即白细胞介素 （IL）-18 和 IL-1β）的成熟和释放。然而，由 NLRP3 炎性小体介导的炎症反应在先天免疫防御和细胞稳态中表现出双重功能。NLRP3 炎性小体的异常激活在各种角膜疾病的病因和病理生理学中很重要。角膜碱烧伤可通过激活 NLRP3 炎性小体诱导焦亡、中性粒细胞浸润和角膜血管生成。当各种病原体侵入角膜时，NLRP3 炎性小体识别病原体相关分子模式或损伤相关分子模式，参与促炎和抗炎机制。此外，由 NLRP3 炎性小体介导的慢性炎症和促炎级联反应有助于糖尿病性角膜病的发病机制。此外，活性氧的过量产生、线粒体功能障碍和 toll 样受体介导的核因子 kappa B 激活驱动 NLRP3 炎性小体的刺激并参与干眼症的进展。然而，关于 NLRP3 炎性小体的调节途径仍然存在争议。 在这篇综述中，我们主要通过使用动物模型的研究，全面概述了 NLRP3 炎性小体在角膜疾病中功能及其调节途径的最新进展。此外，我们探索了与 NLRP3 相关的药理学靶向途径的前景。