Background: Diabetic retinopathy (DR) is a leading cause of blindness in the adult population. Luo-Tong Formula (LTF), a traditional Chinese medicine prescription, has been frequently employed in the treatment of DR. However, the ability of LTF to prevent retinal injury and disease progression, as well as potential mechanisms, remain unknown.

Objectives: To investigate the effect of LTF in alleviating DR and uncover the potential hub targets.

Methods: An experimental DR model was established to assess the effect of LTF and elucidate its underlying mechanism. Retinal thickness, morphological changes of retinal microvessels, as well as the numbers of endothelial cells and pericyte ghosts, were examined. Methylation status was evaluated with methylated DNA immunoprecipitation processing. Bioinformatic analysis of array results was used to screen hub genes. Interactions between potential targets and active compounds were assessed by molecular docking. ADMET analysis was used to evaluate drug-likeness characteristics and toxicity. Molecular dynamics (MD) simulation and MMGBSA calculation of binding free energies were conducted for the optimal core active compound-target complexes obtained by molecular docking.