Therapeutic Effect of Topical Adiponectin in a Mouse Model of Desiccating Stress-Induced Dry Eye

PURPOSE. To investigate the therapeutic effect of topical adiponectin in a mouse model of experimental dry eye (EDE). METHODS. EDE was created by desiccating stress in 6- to 8-week old female C57BL/6 mice. Eye drops consisting of 0.0001%, 0.001%, or 0.01% adiponectin, or balanced salt solution (BSS), were applied in EDE. Tear volume and corneal irregularity score were measured at 5 and 10 days after treatment. Levels of interleukin (IL)-1 beta, IL-6, tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, and monokine induced by interferon-gamma (MIG) were measured in the conjunctiva and lacrimal gland using a multiplex immunobead assay at 10 days. Periodic acid-Schiff staining, immunohistochemistry, and flow cytometry were also performed. RESULTS. Mice treated with 0.001% or 0.01% adiponectin showed a significant improvement in tear volume and corneal irregularity compared with the EDE control and BSS-treated groups. A significant decrease in the levels of IL-1 beta, IL-6, TNF-alpha, IFN-gamma, and MIG and staining intensity of TNF-alpha was observed in the 0.001% and 0.01% adiponectin-treated groups, compared with the other groups, in the conjunctiva and lacrimal gland. In the 0.001% and 0.01% adiponectin-treated groups, the density of conjunctival goblet cells was higher and the number of CD4+CXCR3+T cells was lower than in the other groups. However, there were no significant differences in all parameters between the 0.0001% adiponectin and control groups. CONCLUSIONS. Topical application of adiponectin can markedly improve clinical signs and decrease inflammation in the ocular surface and lacrimal gland of EDE, suggesting that adiponectin eye drops may be used as a therapeutic agent for dry eye disease. (Invest Ophthalmol Vis Sci. 2013;54:155-162) DOI: 10.1167/iovs.12-10648