Effect of Hypotonic 0.18% Sodium Hyaluronate Eyedrops on Inflammation of the Ocular Surface in Experimental Dry Eye

Purpose: To investigate the efficacy of hypotonic 0.18% sodium hyaluronate (SH) eyedrops in a mouse model of experimental dry eye (EDE). Methods: EDE was induced in C57BL/6 mice by a subcutaneous scopolamine injection and an air draft. The mice were divided into 4 groups according to topical treatment regimens: EDE control, isotonic 0.5% carboxymethycellulose (CMC), isotonic 0.1% SH, and hypotonic 0.18% SH. Tear volume, corneal smoothness, and corneal staining scores were measured at 5 and 10 days of EDE. Multiplex immunobead assay, immunohistochemistry, and flow cytometry for proinflammatory cytokines, chemokines, and inflammatory molecules were performed at 10 days of EDE. Results: The 0.18% SH group had a significantly lower corneal smoothness and staining scores than the 0.5% CMC and 0.1% SH groups at 10 days of EDE (P < 0.05). The 0.18% SH group showed significantly low levels of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta, monokine induced by interferon-gamma, and interferon-gamma-inducible protein 10 compared with the other groups (P < 0.05). The mean percentages of CD4(+) CXCR3(+), CD40(+), and CD44(+) cells in the conjunctiva were significantly lower in the 0.18% SH group than in the other groups (P < 0.05). In addition, the 0.1% SH group showed lower levels of TNF-alpha and IL-1 beta and percentages of CD40(+) and CD44(+) cells than the EDE and 0.5% CMC groups. Conclusions: Hypotonic 0.18% SH eyedrops are more effective in improving ocular surface irregularity and staining and decreasing inflammatory cytokines, chemokines, and cells on the ocular surface compared with isotonic 0.5% CMC or 0.1% SH eyedrops in the treatment of EDE.