Inflammatory signals from photoreceptor modulate pathological retinal angiogenesis via c-Fos

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Inflammatory signals from photoreceptor modulate pathological retinal angiogenesis via c-Fos

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Title: Inflammatory signals from photoreceptor modulate pathological retinal angiogenesis via c-Fos
Author: Sun, Ye; Lin, Zhiqiang; Liu, Chi-Hsiu; Gong, Yan; Liegl, Raffael; Fredrick, Thomas W.; Meng, Steven S.; Burnim, Samuel B.; Wang, Zhongxiao; Akula, James D.; Pu, William T.; Chen, Jing; Smith, Lois E.H.

Note: Order does not necessarily reflect citation order of authors.

Citation: Sun, Y., Z. Lin, C. Liu, Y. Gong, R. Liegl, T. W. Fredrick, S. S. Meng, et al. 2017. “Inflammatory signals from photoreceptor modulate pathological retinal angiogenesis via c-Fos.” The Journal of Experimental Medicine 214 (6): 1753-1767. doi:10.1084/jem.20161645. http://dx.doi.org/10.1084/jem.20161645.
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Abstract: Pathological neovessels growing into the normally avascular photoreceptors cause vision loss in many eye diseases, such as age-related macular degeneration and macular telangiectasia. Ocular neovascularization is strongly associated with inflammation, but the source of inflammatory signals and the mechanisms by which these signals regulate the disruption of avascular privilege in photoreceptors are unknown. In this study, we found that c-Fos, a master inflammatory regulator, was increased in photoreceptors in a model of pathological blood vessels invading photoreceptors: the very low-density lipoprotein receptor–deficient (Vldlr−/−) mouse. Increased c-Fos induced inflammatory cytokines interleukin 6 (IL-6) and tumor necrosis factor (TNF), leading to activation of signal transducer and activator of transcription 3 (STAT3) and increased TNFα–induced protein 3 (TNFAIP3) in Vldlr−/− photoreceptors. IL-6 activated the STAT3/vascular endothelial growth factor A (VEGFA) pathway directly, and elevated TNFAIP3 suppressed SOCS3 (suppressor of cytokine signaling 3)–activated STAT3/VEGFA indirectly. Inhibition of c-Fos using photoreceptor-specific AAV (adeno-associated virus)-hRK (human rhodopsin kinase)–sh_c-fos or a chemical inhibitor substantially reduced the pathological neovascularization and rescued visual function in Vldlr−/− mice. These findings suggested that the photoreceptor c-Fos controls blood vessel growth into the normally avascular photoreceptor layer through the inflammatory signal–induced STAT3/VEGFA pathway.
Published Version: doi:10.1084/jem.20161645
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5461000/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:34651857
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