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K. Xu, J. Y. Huang, Z. Saad, N. Gao, C. S. Chen, F.-S. X. Yu; Perturbed EGFR-AKT and -ERK Signaling Pathways Contribute to Impaired Corneal Epithelial Wound Healing in Diabetes Rats. Invest. Ophthalmol. Vis. Sci. 2010;51(13):370.
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The study sought to investigate wound healing and cell signal transduction in corneal epithelium of type I diabetes mellitus (DM) rats rendered by streptozotocin.
The DM rats were used six months after stable nontoxic diabetic state and weight matched normal rats were surgically removed entire corneal epithelium. These wounds extended from limbal to limbal margin without any damages to the gray limbal zone for sublimbal corneal epithelial debridement wound. Corneal wound healing was monitored by fluorescein staining 24 or 48h after epithelial debridement. The distributions of phosphorylation (p) EGFR (Tyr1068) and pAKT (Ser473) in the migrating and healing corneal epithelium were examined by immunofluorescence. The cell signaling pathways of EGFR-AKT and -ERK in corneal epithelial cells during wound healing were evaluated by Western blotting. Cellular apoptosis in corneal epithelium was evaluated by ApopTag plus fluorescein in situ apoptosis detection kit (TUNEL) staining.
Corneal epithelial wound closures in DM rats were significantly delayed 48h after debridement wound compared with that in weight matched control. There were diminished responses of pEGFR (Tyr1068) in the stromal keratocytes underlining the migrating corneal epithelium and decreased cellular staining of pEGFR (Tyr1068) in the healing epithelium in DM rats. Weakening of pAKT (Ser473) staining was also found in the wound leading edge, migrating sheet as well as in non-wounded corneal epithelium in DM rats. Furthermore, disturbed cell responses in EGFR-AKT and -ERK signaling were observed by Western blotting in DM rat corneal epithelial cell lysate. Finally, decreases in pBAD (Ser136, Ser112) and increases in cellular apoptosis in rat corneal epithelium were seen in DM but not control rats.
Perturbed EGFR-AKT and -ERK signaling pathways contribute to increased cellular apoptosis and impaired corneal epithelial wound healing in DM rats.
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