Abstract
Purpose :
To investigate the roles and mechanisms of the vasoactive intestinal polypeptide (VIP) in the regulation of corneal epithelial wound healing, inflammation response, and nerve regeneration in diabetic mice
Methods :
C57BL/6 mice underwent induction of type 1 diabetic mellitus with the intraperitoneal injections of streptozotocin. C57BL/6 mice were treated with resiniferatoxin (RTX) eye drops, known to temporarily abolishing sensory nerve in the corneas. Mouse corneal epithelial wound was created by scraping and treated with VIP and VIP receptor (VPAC1) antagonist to assess their effects on wound healing. Quantitative real-time PCR, western blotting, and immunohistochemistry were used to investigate the influences of VIP on corneal epithelial wound healing, inflammatory response and nerve regeneration in diabetic and RTX treated mouse corneas
Results :
In mouse corneas, the wound-induced expression of VIP was suppressed in diabetic mice. Exogenous VIP promoted corneal epithelial wound healing in normal, diabetic and RTX treated mice. VIP treatment resulted in the upregulation of Sonic hedgehog (SHH), NGF, EGF and nerve regeneration in diabetic mouse corneas. Administration of VIP decreased neutrophils and macrophages infiltration and downregulated the expression of IL-1β and CXCL-2 in diabetic corneas. In addition, VIP enhanced corneal nerve regeneration and upregulated IL-10 and downregulated IL-1β and CXCL-2 expression in RTX treated mice. In normal corneas, the wound healing rate was significantly lowered by the VPAC-1 antagonist
Conclusions :
Neuropeptide VIP through VPAC1 regulates corneal epithelial wound healing, inflammatory response, and nerve regeneration in the diabetic mice, suggesting a therapeutic potential for these molecules in treating diabetic keratopathy
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.