Evaluation of the effectiveness of topical insulin on corneal epithelial healing in rats with neurotrophic keratopathy

Objective: This study aimed to evaluate the dose-dependent effects of topical insulin on corneal epithelial healing, tear production, inflammation, hemorrhage, vascularization, and immunohistochemical markers (Insulin Growth Factor and beta-catenin) in rats modeled with neurotrophic keratopathy. Method: Twenty-eight female Wistar rats were used in the study. A neurotrophic keratopathy model was induced with subcutaneous capsaicin, followed by a total corneal epithelial defect. The rats were divided into four groups: control and treatment groups (0.5 U/ml, 1 U/ml, and 2 U/ml topical insulin groups). The control group received Phosphate Buffered Saline (PBS), while the other groups received topical insulin six times daily at the indicated doses. Tear measurements were performed using the Modified Schirmer test, histopathological evaluations were performed using Hematoxylin-Eosin staining, and immunohistochemical analyses were performed using Insulin Growth Factor and beta-catenin antibodies. Findings: Topical insulin application increased tear secretion at all doses (p<0.01). Corneal epithelial healing was more pronounced, and inflammation and hemorrhage levels were lower in the 0.5 U/ml and 1 U/ml groups (p<0.01). Increased vascularization and inflammation were observed with higher doses. IGF and β-catenin expressions differed significantly between the groups (p<0.01). Conclusion: Topical insulin promotes corneal healing in a dose-dependent manner in the neurotrophic keratopathy model. Doses of half and one U/ml were found to provide the most optimal therapeutic effect, while doses of two U/ml increased the inflammatory response. Further studies are needed to determine the optimum dose. Keywords: β-catenin, IGF, β, corneal healing, neurotrophic keratopathy, topical insulin