esculetin and Dry-Eye-Syndromes

Dry eye formation often originates from oxidative damage to the ocular surface, which can be caused by external environment or internal pathologic factors. Esculetin (6, 7-dihydroxycoumarin) is a natural product found in many plants, and has been reported to have multiple pharmacological activities. The objective of our present study is to investigate if esculetin could protect the corneal epithelial cells from oxidative damages and its underlying antioxidant molecular mechanisms. Our experimental results demonstrated that pretreatment with esculetin markedly increased the cell viability while decreased the apoptosis in H

Topics: Apoptosis; Cell Survival; Cells, Cultured; Dry Eye Syndromes; Epithelium, Corneal; Gene Expression Regulation; Humans; NF-E2-Related Factor 2; Oxidative Stress; RNA; Signal Transduction; Umbelliferones

PurposeIn this study, we investigated the therapeutic effects of topical Esculetin for dry eye rabbits through the ocular tests, inflammatory factor levels and specific phosphorylated protein expressions of ERK1/2 singnal pathway.Patients and methodsThirty-two healthy adult male New Zealand white rabbits were chosen for the study. DES models were established after removing of the main lacrimal gland, Harderian gland and nictitating membrane in the left eyes and randomly divided into group DES control, group CsA, group Esculetin and group Esculetin combined with CsA (C&E), meanwhile the right eyes served as group Normal control. Schirmer's I tests, fluorescein scores, goblet cell densities, inflammatory cytokines IL-1α,IL-1β,TNF-αlevels were observed by slit-lamp microscope, conjunctival impression cytology and ELISA essay at week 0, 1, 2, 4, 8. Phosphorylated-ERK1/2 expressions were detected in Western blot analysis at week 8.ResultsAfter induction of DES, aqueous tear production and goblet cell density were decreased, FL score was much higher in group DES control throughout the study (P<0.05). Both topical Esculetin and Esculetin combing CsA increased the SIT values (10±1 mm, 14±3 mm, P<0.05) and goblet cell densities (77±12/HP, 92±12/HP, P<0.05), decreased FL scores (7.48±0.33, 5.09±0.24, P<0.05) at week 8. Alternations of IL-1α,IL-1β,TNF-αlevels had similar trend. In Western blot analysis, downregulations of p-ERK1/2 were observed in therapy groups when compared with group DES control and the most decreasing was found in group C&E (P<0.05).ConclusionTopical Esculetin improved DES symptoms, downregulated the inflammatory cytokine expressions, suppressed the ERK1/2 pathway and enhanced the therapeutic effect of CsA.

Topics: Administration, Topical; Animals; Antioxidants; Blotting, Western; Conjunctiva; Cornea; Cytokines; Disease Models, Animal; Dose-Response Relationship, Drug; Dry Eye Syndromes; Enzyme-Linked Immunosorbent Assay; Lacrimal Apparatus; Male; Ophthalmic Solutions; Rabbits; Tears; Umbelliferones