Abstract
Retinal vascular endothelial growth factor (VEGF) increased by neovascularization is well known as a pathogenic factor in ocular neovascular diseases. However, it is still unclear how retinal neurons are damaged by VEGF. The aims of this study are to demonstrate the inflammatory protein expression regulated by VEGF using mouse photoreceptor-derived cells and the protective effect of quercetin against VEGF-induced inflammatory response. Expression and phosphorylation of protein and expression of mRNA were detected by immunoblot and reverse transcriptase polymerase chain reaction. VEGF-induced degradation of limiting membrane and translocation of nuclear factor kappa B (NF-κB) were analyzed by immunocytochemistry. VEGF treatment activated angiogenic signaling pathway in photoreceptor cells. In addition, adhesion molecules and matrix metalloproteinases were increased in VEGF-treated photoreceptor cells. All these events were reversed by quercetin. Zona occludins-1 and β-catenin decreased by VEGF were recovered by quercetin. NF-κB signaling pathway regulated by VEGF through phosphorylations of mitogen-activated protein kinases (MAPK) and protein kinase B (Akt) was suppressed by quercetin. These results suggest that quercetin suppressed VEGF-induced excessive inflammatory response in retinal photoreceptor cells by inactivation of NF-κB signals through inhibition of MAPKs and Akt. These data may provide a basic information for development of pharmaceuticals or nutraceuticals for treatment of retinal diseases caused by excessive VEGF.
Highlights
Photoreceptor in retina absorbs light and converts it to stimulate biochemical neurotransmission through the visual cycle, called visual function
We examined the expression of vascular endothelial growth factor (VEGF), VEGF receptor 1 (VEGFR1), and VEGFR2 in 661W cells after VEGF treatment
VEGF treatment resulted in increased phosphorylation of IKKαβ (*** p < 0.001) and IκBα (* p < 0.05) and degradation of IκBα (* p < 0.05) compared to controls (Figure 6E–G), and quercetin treatment recovered the changes of pIKKαβ (### p < 0.001), pIκBα (# p < 0.05), and IκBα (### p < 0.001). These results indicate that the quercetin-mediated inhibition of intracellular adhesion molecule 1 (ICAM1), vascular adhesion molecule 1 (VCAM1), and matrix metalloproteinases (MMP) expression levels was regulated by the NF-κB pathway in VEGF-stimulated 661W cells
Summary
Photoreceptor in retina absorbs light and converts it to stimulate biochemical neurotransmission through the visual cycle, called visual function. Neovascularization (NV) of retina or choroid in sever retinal diseases such as diabetic retinopathy and age-related macular degeneration (AMD) shows proliferative new vessels from the deep capillaries that penetrate into the subretinal space [1]. These rapid unregulated ocular angiogenesis, fragile and leaky vasculature lead to hemorrhage and accumulation of fluids and proteins exudates in ocular cavities and cause impairment of the structure and function of retinal neurons exacerbating visual function of photoreceptor, regarding as a pathologic factor of visual impairment [3,4]
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