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

• Published in: Pharmaceutics Vol. 15; no. 1; p. 78
• Main Authors: Lee, In-Kyung, Yoon, Kyung-Chul, Kang, Seong-Soo, Seon, Su-Kyung, Lee, Kwanghyun, Kim, Brian B
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 26.12.2022; MDPI
• Subjects: (PEG)-BHD1028; adiponectin; Animals; anti-apoptosis; anti-inflammation; Apoptosis; Cornea; dry eye disease (DED); epithelial cell protection; Eye diseases; Homeostasis; Peptides; AdipoR2; AdipoR1; adiponectin; anti-apoptosis; (PEG)-BHD1028; peptide drug; adiponectin receptors; dry eye disease (DED); epithelial cell protection; anti-inflammation
• ISSN: 1999-4923; 1999-4923
• DOI: 10.3390/pharmaceutics15010078

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.