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

Autor: Sean M. Silverman, Rafael Villasmil, Lian Zhao, Maria M Campos, Wai T. Wong, Juan Amaral, Wenxin Ma
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Retinal degeneration
retina
Mouse
microglia
Apoptosis
Synaptic Transmission
Neovascularization
Macular Degeneration
chemistry.chemical_compound
Immunology and Inflammation
0302 clinical medicine
Transforming Growth Factor beta
Biology (General)
Mice
Knockout
Microglia
General Neuroscience
Retinal Degeneration
neurodegeneration
General Medicine
TGF
Choroidal neovascularization
medicine.anatomical_structure
Medicine
medicine.symptom
neovascularization
Research Article
Signal Transduction
QH301-705.5
Science
Ependymoglial Cells
Mice
Transgenic
General Biochemistry
Genetics and Molecular Biology
03 medical and health sciences
medicine
Animals
age-related macular degeneration
Neuroinflammation
Retina
General Immunology and Microbiology
business.industry
Receptor
Transforming Growth Factor-beta Type II
Retinal
medicine.disease
Choroidal Neovascularization
eye diseases
030104 developmental biology
chemistry
sense organs
business
Neuroscience
030217 neurology & neurosurgery
Transforming growth factor
Zdroj: eLife, Vol 8 (2019)
eLife
Popis: 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.
Databáze: OpenAIRE
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