Impact of the Controlled Release of a Connexin 43 Peptide on Corneal Wound Closure in an STZ Model of Type I Diabetes: e86570

• Published in: PloS one 2014-01, Vol.9 (1)
• Main Authors: Moore, Keith, Ghatnekar, Gautam, Gourdie, Robert G, Potts, Jay D
• Format: Article
• Language: English
• ISSN: 1932-6203
• DOI: 10.1371/journal.pone.0086570

The alpha-carboxy terminus 1 ( alpha CT1) peptide is a synthetically produced mimetic modified from the DDLEI C-terminus sequence of connexin 43 (Cx43). Previous research using various wound healing models have found promising therapeutic effects when applying the drug, resulting in increased wound healing rates and reduced scarring. Previous data suggested a rapid metabolism rate in vitro, creating an interest in long term release. Using a streptozotocin (STZ) type I diabetic rat model with a surgically induced corneal injury, we delivered alpha CT1 both directly, in a pluronic gel solution, and in a sustained system, using polymeric alginate-poly-l-ornithine (A-PLO) microcapsules (MC). Fluorescent staining of wound area over a 5 day period indicated a significant increase in wound closure rates for both alpha CT1 and alpha CT1 MC treated groups, with alpha CT1 MC groups showing the most rapid wound closure overall. Analysis of inflammatory reaction to the treatment groups indicated significantly lower levels of both Interferon Inducible T-Cell Alpha Chemoattractant (ITAC) and Tumor Necrosis Factor Alpha (TNF alpha ) markers using confocal quantification and ELISA assays. Additional analysis examining genes selected from the EMT pathway using RT-PCR and Western blotting suggested alpha CT1 modification of Transforming Growth Factor Beta 2 (TGF beta 2), Keratin 8 (Krt8), Estrogen Receptor 1 (Esr1), and Glucose Transporter 4 (Glut4) over a 14 day period. Combined, this data indicated a possible suppression of the inflammatory response by alpha CT1, leading to increased wound healing rates.