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Dry eye disease (DED) is characterized by impaired tear dynamics, leading to complex pathophysiological conditions. (PEG)-BHD1028, a peptide agonist to AdipoRs, was evaluated as a potential therapeutic agent for DED based on the reported physiological function of adiponectin, including anti-inflammation and epithelial protection. Therapeutic effects of (PEG)-BHD1028 were evaluated in experimentally induced EDE with 0.001%, 0.01%, and 0.1% (PEG)-BHD1028 in mice and 0.1%, 0.2%, and 0.4% in rabbits for 10 days. In the rabbit study, 0.05% cyclosporine was also tested as a comparator. The results from the mouse study revealed significant improvement in tear volumes, tear breakup time (TBUT), inflammation, and corneal severity score (CSS) within 10 days at all (PEG)-BHD1028 concentrations. In the rabbit study, the tear volume and TBUT significantly increased in (PEG)-BHD1028 groups compared with vehicle and 0.05% cyclosporine groups. The CSS, apoptosis rate, and corneal thickness of all (PEG)-BHD1028 and 0.05% cyclosporine groups were significantly improved relative to the vehicle group. The immune cell counts of 0.2% and 0.4% (PEG)-BHD1028 treated groups were significantly lower than those of the vehicle group. These results represent the potential of (PEG)-BHD1028 as an effective therapeutic agent for DED.

pharmaceutics

Enhanced Immunomodulation, Anti-Apoptosis, and Improved Tear Dynamics of (PEG)-BHD1028, a Novel Adiponectin Receptor Agonist Peptide, for Treating Dry Eye Disease