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

In-Kyung Lee; Kyung-Chul Yoon; Seong-Soo Kang; Su-Kyung Seon; Kwanghyun Lee; Brian B Kim

doi:10.3390/pharmaceutics15010078

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

Pharmaceutics. 2022 Dec 26;15(1):78. doi: 10.3390/pharmaceutics15010078.

Authors

In-Kyung Lee¹, Kyung-Chul Yoon², Seong-Soo Kang³, Su-Kyung Seon³, Kwanghyun Lee⁴, Brian B Kim¹

Affiliations

¹ EncuraGen, Inc., Anyang 14058, Republic of Korea.
² Department of Ophthalmology, Research Institute of Medical Sciences, Chonnam National University Medical School and Hospital, Gwangju 61469, Republic of Korea.
³ Biomaterial R&BD Center, Chonnam National University, Gwangju 61186, Republic of Korea.
⁴ Department of Ophthalmology, National Health Insurance Service Ilsan Hospital, Goyang-si 10444, Republic of Korea.

Abstract

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.

Keywords: (PEG)-BHD1028; AdipoR1; AdipoR2; adiponectin; adiponectin receptors; anti-apoptosis; anti-inflammation; dry eye disease (DED); epithelial cell protection; peptide drug.

Grants and funding

This research received no external funding.