Abstract
Abstract: :
Purpose:To investigate the role of mono and dinucleotides in the rate of superficial corneal epithelial wound healing. Methods:White rabbits were anaesthetised and wounds were inflicted by topically applying Whatman paper discs (3 mm diameter) soaked in n-heptanol. Wound diameter was measured every 2 hours by means of fluorescein application and cobalt blue light observation on a biomicroscope connected to a CCD camera and managed with the IMAGENET system from Topcon. Agents (10 nmols) were applied topically ten hours after wounding. Results:Control experiments demonstrated that the normal wound-healing rate was 72.4 2.2 µm/hour. Following application of the mononucleotides, ATP and UTP, they accelerated wound healing, inducing healing rates of 89.5 1.3 µm/hour and 120.8 3.5 µm/hour, respectively. Neither UDP nor ADP had a significant effect. Diadenosine tetraphosphate (Ap4A) also increased the wound healing rate to 93.73.2 µm/hour. Following application of diadenosine triphosphate (Ap3A) and diadenosine pentaphosphate (Ap5A) the healing rates were 67.5 2.4 µm/hour and 78.7 1.9 µm/hour, respectively. Application of the MAPK cascade inhibitors genistein, U-0126 and AG-1478, reversed the effects of Ap4A, ATP and UTP. The P2-receptor antagonists, suramin, reactive blue 2, but not PPADS, inhibited wound healing and blocked the effects of Ap4A, ATP and UTP. Conclusion:UTP and Ap4A may be useful compounds for the treatment of superficial (epithelial) lesions such as those caused by mild burns or contact lens scratching. Blocking the effects with P2 antagonists indicates that nucleotides in tear fluid may act as endogenous wound healing agents.
Keywords: 631 wound healing • 372 cornea: epithelium • 541 receptors: pharmacology/physiology