AG1295 Attenuates High-Glucose-Induced Proliferation,Migration,Phenotype Transition,and Interleukin-6 Expression in Human Corneal Stromal Fibroblasts

Abstract

Purpose:

Up to 46%–64% of individuals with diabetes exhibit corneal abnormalities, including epithelial dysfunction and reduced sensitivity, which may gradually impair corneal transparency. Corneal fibroblasts regulate scar formation and play a critical role in maintaining corneal transparency. This study investigated the effects of high-glucose levels on fibroblasts and elucidated the underlying mechanisms.

Methods:

Human corneal stromal fibroblasts were isolated by collagenase digestion of fresh corneal stromal lenticules, obtained from small incision corneal lens extraction surgery, and cultured with different glucose concentrations (5.5–30 mM). The phosphorylated platelet-derived growth factor receptor beta (p-PDGFRβ)/PDGFRβ) ratio, fibroblast proliferation, migration, fibrotic markers, and interleukin-6 (IL-6) expression were assessed.

Results:

Human corneal stromal fibroblast proliferation increased with increasing glucose concentrations, and a glucose concentration of 30 mM was selected for subsequent high-glucose treatment experiments. The p-PDGFRβ/PDGFRβ ratio, fibroblast proliferation, migration, fibrotic markers, and IL-6 expression were enhanced in the high-glucose group compared with those in the control group. These effects were inhibited by treatment with AG1295, a PDGFRβ tyrosine kinase inhibitor.

Conclusions:

In patients with diabetes, fibroblasts may aggregate at sites of corneal injury, potentially promoting scar hyperplasia and reducing corneal transparency. These changes may be reversed by PDGFRβ phosphorylation inhibitors, suggesting new therapeutic avenues.