Puerarin regulates neovascular glaucoma through pigment epithelium-derived growth factor-induced NF-kappa B signaling pathway

摘要

Neovascular glaucoma is an ophthalmic disease and a potentially blinding secondary glaucoma caused by the formation of abnormal new blood vessels on the iris, which can prevent the normal drainage of water from the anterior segment of the eye. Evidence from China has suggested that puerarin benefits many diseases including myocardial infarction, stable angina, cerebral ischemia and glaucoma in a clinical setting. In the present study, the aim was to investigate the efficacies of puerarin on neovascular glaucoma in a mouse model. The molecular mechanism of puerarin-mediated treatment for neovascular glaucoma was also investigated both in vitro and in vivo. Inflammatory responses in mice with neovascular glaucoma were analyzed by western blotting. Oxidative stress levels were investigated following treatment with puerarin in a mouse model of neovascular glaucoma. The results indicated that puerarin markedly improved growth of vascular endothelial cells. The present study reported that puerarin treatment markedly decreased interleukin (IL)-1, IL-17A and tumor necrosis factor- expression levels in mice with neovascular glaucoma. It was found that puerarin significantly decreased oxidative stress levels by reducing reactive oxygen species, superoxide dismutase and malondialdehyde levels, as well as neuronal nitric oxide synthase (NOS) and inducible NOS expression levels. Results indicated that expression levels of pigment epithelium-derived growth factor were significantly inhibited following treatment with puerarin. Mechanism analysis demonstrated that treatment with puerarin effectively inhibited nuclear factor (NF)-B activity and its target protein levels p65, inhibitor of NF-B kinase subunit and inhibitor of NF-B kinase subunit in vascular endothelial cells. Increasing endothelial-derived growth factor (EDGF) expression levels could stimulate NF-B activity and abolish the inhibitory effects of puerarin. An animal study reported that puerarin treatment presented therapeutic effects for mice with neovascular glaucoma. Numbers of new vessels in iris were recovered to normal following puerarin treatment. In conclusion, these results indicated that puerarin treatment can inhibit inflammatory responses and oxidative stress, platelet-derived growth factor (PDGF) expression and NF-B activity, suggesting puerarin may be a potential agent for the treatment of neovascular glaucoma through PDGF-induced NF-B signaling pathway.