Altered expression of genes related with angiogenesis and oxidative stress during the development of oxygen-induced retinopathy in newborn mice / 中国药理学通报

ABSTRACT

Aim To observe the retinal angiogenesis and detect the altered expression of genes related with angiogenesis and oxidative stress during the develop-ment of oxygen-induced retinopathy ( OIR) in newborn mice. Methods OIR was established in newborn mice according to the protocol of Smith et al. Newborn mice at 7 days old were placed into 75 . 5% oxygen for up to 5 days, and then they were put in room air for another 5 days. Retinal neovascularization was ob-served by immunofluorescence staining with cluster of differentiation 31 ( CD31 ) . Gene expression was de-tected using Real-time PCR analysis. Retinal CD31 immunofluorescence staining assay showed that relative hypoxia induced retinal neovascularization in OIR mice after hyperoxia-induced subside of retinal microvascu-lar. Results Real-time PCR analysis showed that vas-cular endothelial growth factor ( VEGF) and its recep-tor ( VEGFR) such as VEGFA, VEGFD, VEGFR1, VEGFR2 gene expression were increased in OIR mouse as compared to control. Platelet-derived growth factor ( PDGF) and its receptor ( PDGFR) such as PDGFA, PDGFB, PDGFRa, PDGFRb gene expression was also increased in OIR mouse as compared to control. Matrix metalloproteinases ( MMPs ) such as MMP2 gene ex-pression were increased in OIR mouse as compared to control. Gene expressions of nuclear factor-related fac-tor ( Nrf2 ) and its downstream genes such as the two subunits of glutamate-cysteine ligase ( GCL)the cata-lytic subunit ( GCLC) and regulatory subunit ( GCLM) were both decreased in OIR mouse as compared to con-trol. Conclusion Our research demonstrates that the expression of genes related with angiogenesis is in-creased in retinas in the development of OIR in mice, whereas the expression of Nrf2 and its downstream genes is all decreased.