Emerging insights into the pathogenesis of retinal vasculitis: Synergistic interactions among inflammatory immunity, neutrophil extracellular traps, and inflammasome-mediated pyroptosis.

Retinal vasculitis is a potentially blinding inflammatory ocular disease whose pathogenesis involves complex interactions among immune dysregulation, vascular endothelial injury, and activation of innate immune responses. This narrative review summarizes recent emerging evidence regarding inflammatory immunity, neutrophil extracellular traps (NETs), inflammasome activation, and pyroptosis in retinal vasculitis. Current evidence suggests that immune complex deposition, Th1/Th17 skewing, and impaired regulatory T-cell (Treg) function may collectively contribute to the establishment of a proinflammatory retinal vascular microenvironment, thereby enhancing neutrophil recruitment and activation through networks of proinflammatory cytokines and chemokines. In parallel, NET-associated components, reactive oxygen species, and damage-associated molecular patterns (DAMPs) may participate in the activation of the NLRP3 inflammasome and Gasdermin D (GSDMD)-mediated pyroptosis, ultimately exacerbating dysfunction of the blood-retinal barrier (BRB) and the neurovascular unit (NVU). Accumulating evidence indicates that inflammatory immunity, NET formation, and inflammasome/pyroptosis signaling may constitute a potential inflammatory amplification network. However, their spatiotemporal relationships and dominant mechanistic roles in retinal vasculitis remain incompletely defined. Notably, most mechanistic evidence is derived primarily from studies of autoimmune uveitis, Behçet"s disease-associated ocular inflammation, experimental autoimmune uveitis (EAU) models, diabetic retinopathy, and non-ocular inflammatory conditions, whereas direct in situ evidence from retinal vasculitic lesions remains limited. Therefore, the NET-inflammasome-pyroptosis axis should currently be regarded as a biologically plausible hypothesis-generating framework rather than a fully established core pathogenic mechanism. Finally, this review discusses potential therapeutic strategies targeting TNF-α, the NLRP3 inflammasome, and NET formation, as well as their translational prospects, with the aim of providing a reference for future mechanistic studies and precision interventions.