TY - JOUR TI - Absence of TGFβ signaling in retinal microglia induces retinal degeneration and exacerbates choroidal neovascularization AU - Ma, Wenxin AU - Silverman, Sean M AU - Zhao, Lian AU - Villasmil, Rafael AU - Campos, Maria M AU - Amaral, Juan AU - Wong, Wai T A2 - Cepko, Constance L A2 - Westbrook, Gary L VL - 8 PY - 2019 DA - 2019/01/22 SP - e42049 C1 - eLife 2019;8:e42049 DO - 10.7554/eLife.42049 UR - https://doi.org/10.7554/eLife.42049 AB - Constitutive TGFβ signaling is important in maintaining retinal neurons and blood vessels and is a factor contributing to the risk for age-related macular degeneration (AMD), a retinal disease involving neurodegeneration and microglial activation. How TGFβ signaling to microglia influences pathological retinal neuroinflammation is unclear. We discovered that ablation of the TGFβ receptor, TGFBR2, in retinal microglia of adult mice induced abnormal microglial numbers, distribution, morphology, and activation status, and promoted a pathological microglial gene expression profile. TGFBR2-deficient retinal microglia induced secondary gliotic changes in Müller cells, neuronal apoptosis, and decreased light-evoked retinal function reflecting abnormal synaptic transmission. While retinal vasculature was unaffected, TGFBR2-deficient microglia demonstrated exaggerated responses to laser-induced injury that was associated with increased choroidal neovascularization, a hallmark of advanced exudative AMD. These findings demonstrate that deficiencies in TGFβ-mediated microglial regulation can drive neuroinflammatory contributions to AMD-related neurodegeneration and neovascularization, highlighting TGFβ signaling as a potential therapeutic target. KW - microglia KW - TGF KW - retina KW - age-related macular degeneration KW - neovascularization KW - neurodegeneration JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -