Inhibition of PRMT5 reduces angiogenesis in a corneal neovascularization model by blocking NLRP3-mediated pyroptosis.

Protein arginine methyltransferase 5 (PRMT5) is a histone methyltransferase crucial for cell proliferation, differentiation, and inflammation. However, the biological functions of PRMT5 and its underlying molecular mechanisms in corneal neovascularization (CNV) remain unclear. This study utilized corneal alkali burn and vascular endothelial growth factor (VEGF)-induced HUVEC models to examine the role of PRMT5 in CNV. We found that PRMT5 expression was significantly upregulated following corneal alkali burn. Experiments both in vitro and in vivo showed that PRMT5 knockdown or inhibition lowered pyroptosis-related protein expression and reduced cell death. PRMT5 interacts with the NACHT domain of NOD-like receptor family pyrin domain-containing 3 (NLRP3) via its Rossmann fold, catalyzing arginine methylation at the R490 and R504 residues through its methyltransferase activity. This process modulates inflammation and pyroptosis, thereby influencing the formation of CNV. In conclusion, our findings provide evidence that inhibiting PRMT5 can alleviate angiogenesis in CNV models by blocking NLRP3-mediated pyroptosis.