Abstract:Ocular surface inflammation constitutes a core pathological mechanism underlying prevalent ocular disorders, including dry eye disease, allergic conjunctivitis, and infectious keratitis. Its pathogenesis is intimately linked to the dysregulated activation of multiple intracellular signaling cascades. This review systematically delineates the pivotal functions of four core signaling pathways—nuclear factor-kappa B(NF-κB), mitogen-activated protein kinase(MAPK), Janus kinase/signal transducer and activator of transcription(JAK/STAT), and the NOD-like receptor protein 3(NLRP3)inflammasome—in the ocular surface inflammation. Specifically, NF-κB functions as a master regulator driving the expression of pro-inflammatory factors; MAPK acts as a central signaling hub that integrates diverse stress stimuli and potentiates inflammatory amplification; JAK/STAT mediates cytokine-driven signal transduction and modulates immune cell differentiation; and NLRP3 senses danger signals and thereby promotes the maturation of inflammatory factors such as interleukin-1β(IL-1β). Notably, these pathways do not function independently but constitute a highly interconnected regulatory network via phosphorylation, and the assembly of transcription factor complexes, which results in limited efficacy of single-targeted therapies due to the reactivation of bypass pathways. Therefore, future treatment for ocular surface inflammation is expected to prioritize multi-target synergistic strategies and personalized precision medicine, thereby enabling more sustained and effective therapeutic options for clinical practice.
