MP322, a plant-derived bioactive compound with potential anti-inflammatory and anti-angiogenic properties, has not yet been investigated for its therapeutic effects on ocular neovascularization and retinal degeneration. In this study, we evaluated the pharmacological activity of MP322 using endothelial cell–based assays and multiple in vivo models of ocular disease.

In cultured endothelial cells, MP322 markedly suppressed hypoxia-induced accumulation of hypoxia-inducible factor-1α (HIF-1α) protein without altering HIF1A mRNA expression, suggesting post-transcriptional regulation. Consistently, MP322 reduced the expression of HIF-1 downstream targets, including VEGFA, EPO, and SLC2A1. Functionally, MP322 significantly attenuated VEGF-A–induced angiogenic responses, including endothelial cell migration, tube formation, and invasion.

The protective effects of MP322 were further validated in vivo. In a murine alkali-induced corneal injury model, oral administration of MP322 (50 or 200 mg/kg) significantly reduced corneal neovascularization and epithelial damage. These effects were accompanied by decreased expression of inflammatory (Tnf, Ninj1), angiogenic (Vegfa), matrix-remodeling (Mmp2, Mmp9), and fibrotic (Acta2) markers. In an N-methyl-N-nitrosourea (MNU)-induced retinal degeneration model, MP322 preserved outer nuclear layer thickness, attenuated GFAP upregulation, restored rhodopsin levels, and suppressed MMP-9 expression. Furthermore, in a laser-induced choroidal neovascularization (CNV) model, MP322 significantly reduced lesion size and VEGF immunoreactivity, along with decreased transcription of Vegfa, Mmp2, Mmp9, and Col1a1.

Collectively, these findings demonstrate that MP322 exerts protective effects against pathological ocular angiogenesis and retinal degeneration through modulation of the HIF-1/VEGF signaling axis and associated inflammatory and fibrotic pathways. These results suggest that MP322 may serve as a promising multi-target therapeutic candidate for vision-threatening ocular diseases.