Effect of Topical 5-Aminoimidazole-4-carboxamide-1-β-d-Ribofuranoside in a Mouse Model of Experimental Dry Eye

PURPOSE. To investigate the efficacy of topical 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR) in a mouse model of experimental dry eye (EDE). METHODS. Eye drops consisting of 0.001% or 0.01% AICAR, 0.05% cyclosporine A (CsA), or balanced salt solution (BSS) were applied for the treatment of EDE. Tear volume, tear film break-up time (BUT), and corneal fluorescein staining scores were measured 10 days after treatment. Levels of interleukin (IL)-1 beta, IL-6, tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, interferon gamma-induced protein 10 (IP-10), and monokine induced by interferon-gamma (MIG) were measured in the conjunctiva. In addition, Western blot, periodic acid-Schiff staining for evaluating goblet cell density, flow cytometry for counting the number of CD4+CXCR3+ T cells, and immunohistochemistry for detection of 4-hydroxy-2-nonenal (4HNE) were performed. RESULTS. Mice treated with 0.01% AICAR showed a significant improvement in all clinical parameters compared with the EDE control, vehicle control, and 0.001% AICAR groups (P < 0.001). A significant decrease in the levels of IL-1 beta, IL-6, TNF-alpha, IFN-gamma, IP-10, and MIG, the number of CD4+CXCR3+ T cells, and the number of 4HNE-positive cells were also observed in the 0.01% AICAR group (P < 0.001). Although 0.05% CsA also led to an improvement in clinical parameters and inflammatory molecule levels, its therapeutic effects were comparable or inferior to those of 0.01% AICAR. CONCLUSIONS. Topical application of 0.01% AICAR can markedly improve clinical signs and decrease inflammation in the ocular surface of EDE, suggesting that AICAR eye drops may be used as a therapeutic agent for dry eye disease.