Specialized Pro-Resolving Mediators at the Ocular Surface: Biosynthesis, Mechanisms, and Therapeutic Potential

Specialized pro-resolving mediators (SPMs) are endogenous lipid mediators that actively orchestrate the resolution of inflammation rather than relying solely on broad suppression of inflammatory signaling. At the ocular surface, lipoxins, resolvins, protectins, maresins, and related pro-resolving mediators regulate epithelial repair, leukocyte responses, angiogenesis, conjunctival goblet-cell secretion, tear-film homeostasis, and corneal nerve regeneration. This review synthesizes evidence for local SPM biosynthesis and receptor signaling in the cornea and conjunctiva, together with tear lipid mediator profiling, with emphasis on anterior-segment and ocular-surface disease models. Particular attention is given to the endogenous lipoxin A4 circuit, resolvin-mediated control of corneal inflammation and viral keratitis, docosanoid regulation of corneal nerve regeneration, SPM modulation of conjunctival goblet-cell mucin secretion, tear lipid mediator signatures, and the translational development of resolvin E1 (RvE1)-based analogs for dry eye disease. Current evidence positions SPMs as mechanistically distinct therapeutic candidates for ocular-surface disease; however, clinical translation will require optimized delivery, biomarker-guided patient selection, and rigorous validation in disease-state cohorts.