resolvin-d1 and Corneal-Injuries

The study aims to investigate the role of the lipid mediator resolvin D1 (RvD1) in bacterial keratitis in a murine model.. The effect of RvD1 on Pseudomonas aeruginosa-stimulated human corneal epithelial cells (HCECs) and mouse macrophages and dendritic cells (DCs) was assessed. C57BL/6 mouse corneas were abraded and treated with RvD1 after stimulation with P. aeruginosa, following which cytokine production level in the cornea and drainage lymph nodes was compared with that in controls. Corneal opacity and thickness were assessed using anterior segment photographs, and optical coherence tomography and corneal infiltrates were analyzed using immunohistochemistry for neutrophils.. RvD1 significantly inhibited pro-inflammatory cytokine production in HCECs, mouse macrophages, and DCs. Corneal opacity and corneal thickness were reduced, and the development of corneal infiltrates, specifically neutrophils, was also significantly inhibited by RvD1 in response to stimulation with P. aeruginosa.. RvD1 inhibits P. aeruginosa-induced corneal inflammation. This finding supports a potential therapeutic approach for patients with bacterial keratitis.

Topics: Animals; Corneal Injuries; Corneal Opacity; Cytokines; Docosahexaenoic Acids; Eye Infections, Bacterial; Humans; Keratitis; Mice; Mice, Inbred C57BL; Pseudomonas aeruginosa; Pseudomonas Infections

To investigate the effect and mechanism of proresolving lipid mediator resolvin D1 (RvD1) on the corneal epithelium and the restoration of mechanical sensation in diabetic mice.. Type 1 diabetes was induced in mice with intraperitoneal streptozocin injections. The healthy and diabetic mice underwent removal of the central corneal epithelium, and then 100 ng/ml RvD1 or its formyl peptide receptor 2 (FPR2) antagonist WRW4 was used to treat the diabetic mice. Regeneration of the corneal epithelium and nerves was observed with sodium fluorescein staining and whole-mount anti-β3-tubulin fluorescence staining. The inflammatory response level was measured with hematoxylin and eosin staining (inflammatory cell infiltration), enzyme-linked immunosorbent assay (tumor necrosis factor alpha and interleukin-1 beta content), myeloperoxidase activity, and fluorescence staining (macrophage content). The reactive oxygen species (ROS) and glutathione (GSH) levels were examined with incubation with fluorescent probes, and oxidative stress-related protein expression levels were evaluated with fluorescence staining and western blotting.. Topical application of RvD1 promoted regeneration of the corneal epithelium in diabetic mice, accompanied by the reactivation of signaling and inflammation resolution related to regeneration of the epithelium. Furthermore, RvD1 directly attenuated the accumulation of ROS and nicotinamide adenine dinucleotide phosphate oxidase 2/4 expression, while RvD1 enhanced GSH synthesis and reactivated the Nrf2-ARE signaling pathway that was impaired in the corneal epithelium in the diabetic mice. More interestingly, topical application of RvD1 promoted regeneration of corneal nerves and completely restored impaired mechanical sensitivity of the cornea in diabetic mice. In addition, the promotion of corneal epithelial wound healing by RvD1 in diabetic mice was abolished by its FPR2 antagonist WRW4.. Topical application of RvD1 promotes corneal epithelial wound healing and the restoration of mechanical sensation in diabetic mice, which may be related to the lipid mediator's regulation of inflammation resolution, the reactivation of regenerative signaling in the epithelium, and the attenuation of oxidative stress.

Topics: Administration, Topical; Animals; Carboxylic Ester Hydrolases; Corneal Injuries; Diabetes Mellitus, Experimental; Docosahexaenoic Acids; Epithelium, Corneal; Gene Expression Regulation; Glutathione; Interleukin-1beta; Male; Mice; Mice, Inbred C57BL; NADH, NADPH Oxidoreductases; NF-E2-Related Factor 2; Oligopeptides; Optic Nerve; Peroxidase; Reactive Oxygen Species; Receptors, Formyl Peptide; Regeneration; Streptozocin; Touch Perception; Tumor Necrosis Factor-alpha; Wound Healing