Targeting the NLRP3 inflammasome: Pharmacological mechanisms for the treatment of dry eye disease.

Dry eye disease (DED) is a multifactorial disorder characterized by tear film instability due to reduced tear secretion, increased evaporation, or the production of poor-quality tears. This imbalance leads to ocular surface inflammation, tissue damage, and aberrant nociception, collectively imposing a substantial burden on patients' quality of life. Emerging evidence highlights the pivotal role of ocular surface inflammation in the pathophysiology of chronic DED. Although current anti-inflammatory therapies offer symptomatic relief, they fail to fundamentally address the underlying pathological mechanisms. The NOD-like receptor protein-3 (NLRP3) inflammasome, a multiprotein complex activated by diverse pathogenic stimuli, has been identified as a key driver of ocular surface inflammation. Targeting the NLRP3 inflammasome represents a promising therapeutic strategy for DED. To date, a comprehensive and systematic review of the relationship between NLRP3 and DED, as well as the therapeutic potential of NLRP3-targeted interventions in DED, remains lacking. Accordingly, we summarize current therapeutic strategies targeting the NLRP3 inflammasome pathway for the treatment of DED, including both traditional Chinese medicines and synthetic compounds, and highlight the potential of NLRP3 inflammasome as a promising therapeutic target within the broader context of anti-inflammatory interventions. We aim to provide novel insights that guide the development of next-generation pharmacological interventions for DED.