Therapeutic Efficacy of Topical Epigallocatechin Gallate in Murine Dry Eye

Abstract

Objective To study the efficacy of topical epigallocatechin gallate (EGCG) for treatment of dry eye disease (DED). Methods Female 7–8 week old C57BL/6 mice were housed in the controlled environment chamber to induce DED. Topical 0.01% or 0.1% EGCG, or vehicle, was applied to the eyes of DED mice. Corneal fluorescein staining and the number of corneal CD11b+ cells were assessed in the different groups. Expression of IL-1β, tumor necrosis factor (TNF)-α, Chemokine ligand 2 (CCL2) and VEGF-A/C/D were evaluated by real-time PCR in the corneas at day 9. Corneas were stained for LYVE-1 to evaluate lympangiogenesis, and the TUNEL assay was used to evaluate apoptosis of corneal epithelial cells. Results Treatment with 0.1% EGCG showed a significant decrease in corneal fluorescein staining compared with the vehicle (24.6%, P=0.001), and untreated controls (41.9%, P<0.001). A significant decrease in the number of CD11b+ cells was observed in 0.1% EGCG treated eyes, compared with the vehicle in the peripheral (23.3%, P=0.001) and central (26.1%, P=0.009) corneas. Treatment with 0.1% EGCG was associated with a significant decrease in the corneal expression of IL-1β (P=0.029), and CCL2 (P=0.001) compared to the vehicle, and in VEGF-A and -D levels compared to the untreated group (P=0.002, P=0.005, respectively). 0.01% EGCG also showed a decrease in inflammation at the molecular level, but no significant changes in the clinical signs of DED. No cellular toxicity to the corneal epithelium was observed with 0.01% or 0.1% EGCG. Conclusions Topical EGCG treatment is able to reduce the clinical signs and inflammatory changes in DED through suppressing the inflammatory cytokines expression and infiltration of CD11b+ cells in the cornea.