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Bohan Xu, Qishan Chen, Xiangke Yin, Weirong Chen, Xuri Li, Rong Ju; VEGFR2 regulates energy metabolism and cell survival in retinal pigment epithelium cells. Invest. Ophthalmol. Vis. Sci. 2018;59(9):4031.
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© ARVO (1962-2015); The Authors (2016-present)
Retinal pigment epithelium (RPE) cells are essential in maintaining retinal homeostasis, and loss of RPE cells leads to the progression of macular degeneration including age-related macular degeneration (AMD). While energy metabolism has been found to be critical for the viability, differentiation and normal physiology of RPE cells, the underlying regulation mechanism remains incomplete understood. In this study, we examined the roles of VEGFR2 in regulation of energy metabolism as well as redox homeostasis of RPE cells.
SiRNA was utilized to knock down VEGFR2 in both ARPE-19 and primary human RPE (hRPE) cells. The survival of the RPE cells was examined in the presence and absence of glucose as well as BPTES, an inhibitor of glutaminolysis. The expression levels of Nrf2, HMOX1, NQ-1, FTL were determined by qPCR and Western Blotting analysis. A VEGFR2 inhibitor was injected intravitreally into mice and expression of HMOX1 was measured.
We found knockdown of VEGFR2 in the primary hRPE cells protected the cells from glucose deprivation-induced cell death. The protective effect was reversed by the glutaminase inhibitor BPTES. Moreover, VEGFR2 knockdown decreased glucose deprivation-mediated expression upregulation of Nrf2 and its downstream targets HMOX1, NQ-1, FTL. Consistently, in vivo, we found that suppression of VEGFR2 kinase activity by injection of an inhibitor reduced the expression level of HMOX1 in both retinae and choroid.
VEGFR2 plays a crucial role in regulating the different pathways of energy production and redox homeostasis to support the cell survival in RPE cells under the glucose deprivation conditions. Our results provide the insights into RPE-related pathogenesis due to insufficient blood supply.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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