Therapeutic Effect of Topical Adiponectin-Derived Short Peptides Compared with Globular Adiponectin in Experimental Dry Eye and Alkali Burn

J Ocul Pharmacol Ther. 2020 Mar;36(2):88-96. doi: 10.1089/jop.2018.0131. Epub 2019 Oct 30.

Abstract

Purpose: To evaluate the efficacy of adiponectin (APN)-derived short peptides (ADPs) 355 compared with globular APN in a mouse model of experimental dry eye (EDE) and corneal alkali burn. Methods: EDE and chemical burn were induced in C57BL/6 mice by desiccating stress and application of NaOH, respectively. Eye drops consisting of 0.01% globular APN, 0.01% ADPs, 0.1% ADPs, or balanced salt solution (BSS) were applied. Tear volume, tear film break-up time, and corneal staining scores were measured. Concentrations of interleukin (IL)-1β, interferon (IFN)-γ, IL-6, CXCL-9, and CXCL-10 using multiplex immunobead assay were evaluated, and flow cytometry were performed. Corneal epithelial defects and haze degree were analyzed, and enzyme-linked immunosorbent assay for IL-1β and transforming growth factor (TGF)-β levels were observed. Results: All treatment groups showed an improvement in clinical parameters and CD4+CCR5+ T cell and CD11b+ cell infiltrations in the conjunctiva (all P < 0.05). Both ADPs groups had significantly decreased concentrations of IL-1β, IFN-γ, IL-6, CXCL-9, and CXCL-10 in the conjunctiva than the EDE or BSS group. Significantly improved parameters of epithelial defect, degree of haze, and concentrations of IL-1β and TGF-β were observed in all treatment groups. However, no significant differences were noted in clinical or experimental parameters among treatment groups. Conclusion: Topical ADPs could effectively improve clinical signs and inflammation of ocular surface in the EDE or alkali burn, and its efficacy and potency were similar to those of globular APN.

Keywords: adiponectin-derived short peptides; alkali burn; dry eye disease; globular adiponectin.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiponectin / administration & dosage
  • Adiponectin / therapeutic use*
  • Administration, Topical
  • Animals
  • Burns, Chemical / drug therapy*
  • Burns, Chemical / metabolism
  • Disease Models, Animal
  • Dry Eye Syndromes / drug therapy*
  • Dry Eye Syndromes / metabolism
  • Eye Burns / chemically induced
  • Eye Burns / drug therapy*
  • Eye Burns / metabolism
  • Female
  • Injections, Subcutaneous
  • Mice
  • Mice, Inbred C57BL
  • Ophthalmic Solutions / administration & dosage
  • Ophthalmic Solutions / therapeutic use*
  • Peptides / administration & dosage
  • Peptides / therapeutic use*
  • Sodium Hydroxide

Substances

  • Adiponectin
  • Ophthalmic Solutions
  • Peptides
  • Sodium Hydroxide