Pro-Resolving Mediators in Ocular Inflammation Management

Pro-resolving mediators are endogenous lipid autacoids that actively orchestrate the cessation of inflammation and restoration of tissue homeostasis. In the eye, balanced inflammatory responses are essential to protect delicate structures such as the cornea, conjunctiva and retina without compromising transparency or neural function. Key classes of pro-resolving mediators include lipoxins, resolvins, protectins and maresins, each derived from polyunsaturated fatty acids. These agents dampen leukocyte infiltration, counter-regulate pro-inflammatory cytokines, modulate glial reactivity and promote epithelial and neuronal repair. In ocular surface disorders—ranging from allergic conjunctivitis and dry eye disease to infectious keratitis—and in posterior segment conditions such as uveitis and glaucoma, pro-resolving mediators offer targeted mechanisms to resolve inflammation without the adverse effects associated with prolonged steroid use. Their action through dedicated G protein-coupled receptors, together with their capacity to stimulate mucin secretion, enhance phagocytosis and support wound closure, underscores their therapeutic promise in preserving vision and ocular integrity across diverse clinical settings.

Research from Nature Portfolio

Recent studies have demonstrated that lipoxin A4 (LXA4) acts directly on human conjunctival goblet cells via the ALX/FPR2 receptor to maintain ocular surface homeostasis. LXA4 elevates intracellular calcium and activates ERK1/2 signalling, thereby enhancing mucin secretion under basal conditions. When applied prior to histamine challenge, LXA4 inhibits histamine-induced increases in calcium flux, mucin release and ERK1/2 activation. These findings reveal a dual role for LXA4 in both promoting tear film stability and curbing allergic-mediator-driven inflammation, highlighting its potential as a novel treatment approach for allergic conjunctivitis and dry eye disease.

Pro-Resolving Mediators in Ocular Inflammation Management publication trend

The graph below shows the total number of articles in pro-resolving mediators in ocular inflammation management across all publications each year (not limited to Nature Index journals).

Technical terms

Pro-resolving mediators: Endogenous lipid-derived compounds that actively terminate inflammation and promote tissue repair.

Lipoxin A4 (LXA4): An arachidonic acid–derived mediator that binds ALX/FPR2 to modulate immune cell responses and restore homeostasis.

Resolvin D1 (RvD1): A docosahexaenoic acid–derived mediator that reduces inflammatory signalling and supports epithelial and neuronal survival.

Conjunctival goblet cells: Mucin-secreting epithelial cells that maintain tear film stability and protect the ocular surface.

Formyl peptide receptor 2 (FPR2/ALX): A G protein-coupled receptor mediating the actions of lipoxins and resolvins on target cells.

References

1. Dysregulation of neuroprotective lipoxin pathway in astrocytes in response to cytokines and ocular hypertension. Acta Neuropathologica Communications (2024).
2. Lipoxin A4 Counter-regulates Histamine-stimulated Glycoconjugate Secretion in Conjunctival Goblet Cells. Scientific Reports (2016).
3. Resolvin D2 and Resolvin D1 Differentially Activate Protein Kinases to Counter-Regulate Histamine-Induced [Ca2+]i Increase and Mucin Secretion in Conjunctival Goblet Cells. International Journal of Molecular Sciences (2021).
4. Resolvin D1 attenuates the inflammatory process in mouse model of LPS‐induced keratitis. Journal of Cellular and Molecular Medicine (2020).