Effects of pituitary adenylate cyclase activating polypeptide (PACAP) in corneal epithelial regeneration and signal transduction in rats

Abstract

Corneal epithelium responds to insults with a rapid wound healing, which is essential for maintaining vision. The proper balance of apoptotic and proliferation-stimulating pathways is critical for normal regeneration. Pituitary adenylate cyclase activating polypeptide (PACAP) is an important growth factor during the development of the nervous system and exerts cytoprotective effects in injuries. The aim of the present study was to investigate the effects of PACAP on corneal epithelial wound healing in rats and on two important protective signaling molecules, Akt and ERK1/2, both of which have been reported to play important roles during cell survival and regeneration, including corneal wound healing. Wistar rats received PACAP treatment in form of eyedrops, containing 1, 5 and 10 µg PACAP27, immediately and every two hours after corneal abrasion. Corneas were stained with fluorescein dye and further processed for histological staining or Western blot analysis for Akt and ERK1/2 expression. Our results showed that topical PACAP application enhanced corneal wound healing, as the area of injury was significantly less in PACAP-treated groups. Furthermore, both ERK1/2 and Akt signaling was induced upon PACAP administration in both injured and intact corneas. In summary, the present results show that PACAP enhances corneal wound healing in a rat model of corneal abrasion.