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Absence of TGF? signaling in retinal microglia induces retinal degeneration and exacerbates choroidal neovascularization.


ABSTRACT: Constitutive TGF? 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 TGF? signaling to microglia influences pathological retinal neuroinflammation is unclear. We discovered that ablation of the TGF? 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 TGF?-mediated microglial regulation can drive neuroinflammatory contributions to AMD-related neurodegeneration and neovascularization, highlighting TGF? signaling as a potential therapeutic target.

SUBMITTER: Ma W 

PROVIDER: S-EPMC6342522 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Absence of TGFβ signaling in retinal microglia induces retinal degeneration and exacerbates choroidal neovascularization.

Ma Wenxin W   Silverman Sean M SM   Zhao Lian L   Villasmil Rafael R   Campos Maria M MM   Amaral Juan J   Wong Wai T WT  

eLife 20190122


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, an  ...[more]

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