Abstract
Diabetes-associated corneal dysfunction involves oxidative stress, epithelial injury and disrupted nerve–epithelial communication, contributing to delayed wound healing and reduced corneal sensitivity. Local formulations combining antioxidant activity with support for ocular surface hydration and epithelial integrity may help preserve corneal homeostasis under metabolic stress. This study evaluated whether a Pycnogenol-based ophthalmic formulation (POF), containing polyphenol-rich pine bark extract, sodium hyaluronate, lipids and vitamins, supports corneal homeostasis in streptozotocin (STZ)-treated pre-hatching chicken embryos. Chemical profiling by mass spectrometry and biocompatibility testing were followed by corneal biochemical, histological, gene-expression and nerve-labelling analyses. Circulating glucose and insulin were measured to contextualize corneal responses. POF was well tolerated under the tested conditions. STZ induced hyperglycaemia, reduced circulating insulin, increased corneal oxidative/metabolic biomarkers and disrupted epithelial organization. Following 3 h of POF exposure, corneal stress biomarkers decreased and epithelial organization improved, without significant changes in circulating glucose or insulin. These effects were accompanied by modulation of inflammatory, matrix-remodelling and vascular endothelial growth factor-related gene expression. Neurotrophic gene expression and the fluorescently labelled nerve-associated area also increased. Overall, these findings support the protective potential of the complete formulation in corneal tissue under diabetes-associated oxidative/metabolic stress.