Abstract
Purpose:
Background: Pathological conditions such as diabetes mellitus delay corneal epithelial wound healing frequently, potentially resulting in persistent corneal defects and recurrent corneal erosion. Transforming growth factor Beta (TGFβs) are key mediators of wound healing. To explore the role(s) of TGFβ isoforms (1, 2 and 3) in corneal epithelial wound healing, we assessed the effect of TGFβ on epithelial wound closure in cultured porcine cornea in the presence of normal or high glucose concentrations.
Methods:
Methods: Genome-wide cDNA array was performed using epithelial cells isolated from normal and diabetic corneas prior to and 40 h post epithelial debridement wound. The array results were verified using RT- and realtime-PCR and immuniohistochemistry. To assess the effects of TGFβ isforms on corneal epithelial wound healing, wounded porcine corneas were cultured in high glucose (25 mM) and treated with recombinant TGFβ1-3.
Results:
Results: The expressions of TGFβ1-3 were elevated in response to wounding and this elevation for TGFβ3 is dampened in diabetic rat corneas. cDNA array analysis revealed several TGFβ targeted genes were also downregulated in diabetic healing CECs. Immunohistochemistry showed that TGFβ3 is highly expressed in entire migrating epithelial sheet in non-diabetic corneas while only a few cells at the leading edge in diabetic cornea. In cultured corneas, TGFβ3, but not TGFβ1, accelerated high glucose delayed epithelial wound closure.
Conclusions:
Conclusion: In type II diabetic corneas, the expression of TGFβ3 but not TGFβ1 response to wound is suppressed by hyperglycemia and TGFβ3, an antifibrosis factor, might be used to treat delayed wound healing in the cornea and potentially in the skin of diabetic patients.
Keywords: 482 cornea: epithelium •
498 diabetes •
424 antioxidants