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B. Liu, Z. Li, L. Faia, R. Nussenblatt; Pro-Angiogenic Effect of IFN Is Dependent on the PI3k/mTOR/Translational Pathway. Invest. Ophthalmol. Vis. Sci. 2009;50(13):1181.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the molecular signaling pathway of the pro-inflammatory cytokine IFNγ contributing to angiogenesis in retinal pigmented epithelial (RPE) cells and the role of mTOR in this process.
Human adult RPE and fetal retinal epithelial cells (fRPE) were used in this study. Real-time polymerase chain reaction was used to detect human VEGF mRNA expression. VEGF expression from cell supernatant was measured using enzyme-linked immunosorbent assay. SDS-PAGE and western blot analysis were used to detect the expression of signaling molecules.
IFNγ promoted human VEGF secretion in both adult and fetal RPE cells. The PI3K/Akt/mTOR/p70 S6 kinase pathway is required for IFNγ angiogenic effectiveness in retinal cells. Both the mTOR inhibitor, rapamycin, and the PI3K inhibitor, LY294002, greatly decreased hVEGF secretion from RPE cells. However, they are unrelated to the regulatory activities of the IFNγ-dependent STAT1 phophorylation/activation. Moreover, IFNγ induced hVEGF expression was not affected by SiRNA targeted to STAT1, implying that the classic JAK-STAT pathway of IFNγ may not be involved in the angiogenic process.
We provide evidence that IFNγ functions as a pro-angiogenic factor in human retina. Our work emphasizes that the activation of the PI3K/mTOR/translational pathway is critical for inflammation mediated angiogenesis in RPE cells. By elucidating molecular signaling involved in this process, our findings provide further mechanistic insight into the successful clinical application of rapamycin therapy for choroidal neovascularization in age related macular degeneration.
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