(+)-a-Longipinene alleviates murine laser-induced choroidal neovascularization: Evidence from in vivo and in vitro experiments.

Choroidal neovascularization (CNV) is a progressive, degenerative pathological change. CNV can lead to severe vision loss, even blindness. (+)-a-Longipinene (LON) is an essential oil isolated from Pinus koraiensis and Hypericum. It plays anti-inflammatory and anti-angiogenic roles. Here, we attempted to identify the role and mechanism of action of (+)-a-LON in a murine model of laser-induced CNV as well as in vitro in hypoxic human choroidal endothelial cells (HCECs). (+)-a-LON alleviated the formation of laser-induced CNV in mice without causing ocular and systemic toxicity. Moreover, (+)-a-LON inhibited the production of fibroblast growth factor 2 (FGF2) in hypoxic human HCECs by downregulating the M3 muscarinic acetylcholine receptor (M3 mAchR)/diacylglycerol (DAG)/protein kinase C alpha (PKCα)/E1A-binding protein P300 (EP300) pathway. Notably, (+)-a-LON inhibited the hypoxia-induced proliferation, migration, and tube formation of HCECs and also suppressed inflammatory responses in the cells by downregulating the M3 mAchR/DAG/PKCα/EP300/FGF2 pathway. Briefly, (+)-a-LON attenuated the symptoms of CNV possibly by blocking the M3 mAchR/DAG/PKCα/EP300/FGF2 pathway in CECs.