The results suggest that 0.5 mM paeoniflorin administered before ischemic injury, may act as a potential adjunctive or alternative therapy for retinal ischemia, utilizing novel mechanisms such as β-catenin, HIF-1α, VEGF, and Ang-2 RNA downregulation, especially in cases where single-pathway therapies (e.g., anti-VEGF) prove ineffective. Here, HIF1A is linked to retinal ischemia.