rhFGF-21 accelerates corneal epithelial wound healing through the attenuation of oxidative stress and inflammatory mediators in diabetic mice

Diabetic Keratopathy (DK), commonly associated with a hyperactive inflammatory response, is one of the most common eye complications of diabetes. The peptide hormone fibroblast growth factor 21 (FGF-21) has been demonstrated to have anti-inflammatory and antioxidant properties. However, whether administration of recombinant human (rh) FGF21 can potentially regulate DK is still unknown. Therefore, in this work we investigated the role of rhFGF-21 in the modulation of corneal epithelial wound healing, the inflammation response, and oxidative stress using type 1 diabetic mice and high glucose–treated human corneal epithelial cells (HCECs). Our experimental results indicated that rhFGF-21 treatment promoted epithelial wound healing, improved tear production, and corneal edema, decreased levels of proinflammatory cytokines TNF-α, IL-6, IL-1β, MCP-1, IFN-γ, MMP-2, and MMP-9 in both diabetic mouse corneal epithelium and high glucose-treated HCECs. Furthermore, we found rhFGF21 treatment inhibited ROS production and increased levels of anti-inflammatory molecules IL-10 and SOD-1, which suggests that FGF-21 has a protective role in diabetic corneal epithelial healing by increasing the antioxidant capacity and reducing the release of inflammatory mediators and MMPs. Therefore, we propose administration of FGF-21 may represent a potential treatment for diabetic keratopathy.