Effect of EGF on the corneal wound healing of alloxan diabetic mice.
ABSTRACT We identified the local treatment effect of epidermal growth factor on corneal wound healing of alloxan diabetic mice. The corneal wounds were induced by 0.5 M NaOH solution on the corneal surfaces of the diabetic and non-diabetic groups. The local epidermal growth factor solution (100 ng ml-1) was dropped in 5-microliters aliquots into the eye twice a day. The corneal wounds were measured daily for 15 days and examined histologically at the end of 15th day of experimental period. The results indicated that topical epidermal growth factor treatment of diabetic and non-diabetic mice greatly improved the incidence of healing of wounded corneas.
Article: High glucose suppresses epidermal growth factor receptor/phosphatidylinositol 3-kinase/Akt signaling pathway and attenuates corneal epithelial wound healing.[show abstract] [hide abstract]
ABSTRACT: Patients with diabetes are at an increased risk for developing corneal complications and delayed wound healing. This study investigated the effects of high glucose on epidermal growth factor receptor (EGFR) signaling and on epithelial wound healing in the cornea. Effects of high glucose on wound healing and on EGFR signaling were investigated in cultured porcine corneas, human corneal epithelial cells, and human corneas using Western blotting and immunofluorescence. Effects of high glucose on reactive oxygen species (ROS) and glutathione levels and on EGFR pathways were assessed in porcine and primary human corneal epithelial cells, respectively. The effects of EGFR ligands and antioxidants on high glucose-delayed epithelial wound healing were assessed in cultured porcine corneas. High glucose impaired ex vivo epithelial wound healing and disturbed cell responses and EGFR signaling to wounding. High glucose suppressed Akt phosphorylation in an ROS-sensitive manner and decreased intracellular glutathione in cultured porcine corneas. Exposure to high glucose for 24 h resulted in an increase in ROS-positive cells in primary human corneal epithelial cells. Whereas heparin-binding EGF-like growth factor and antioxidant N-acetylcysteine had beneficial effects on epithelial wound closure, their combination significantly accelerated high glucose-delayed wound healing to a level similar to that seen in control subjects. Finally, Akt signaling pathway was perturbed in the epithelia of human diabetic corneas, but not in the corneas of nondiabetic, age-matched donors. High glucose, likely through ROS, impairs the EGFR-phosphatidylinositol 3-kinase/Akt pathway, resulting in delayed corneal epithelial wound healing. Antioxidants in combination with EGFR ligands may be promising potential therapeutics for diabetic keratopathy.Diabetes 03/2009; 58(5):1077-85. · 8.29 Impact Factor