| First Author | Ma W | Year | 2019 |
| Journal | Elife | Volume | 8 |
| PubMed ID | 30666961 | Mgi Jnum | J:280436 |
| Mgi Id | MGI:6368234 | Doi | 10.7554/eLife.42049 |
| Citation | Ma W, et al. (2019) Absence of TGFbeta signaling in retinal microglia induces retinal degeneration and exacerbates choroidal neovascularization. Elife 8:e42049 |
| abstractText | Constitutive TGFbeta 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 TGFbeta signaling to microglia influences pathological retinal neuroinflammation is unclear. We discovered that ablation of the TGFbeta 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 Muller 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 TGFbeta-mediated microglial regulation can drive neuroinflammatory contributions to AMD-related neurodegeneration and neovascularization, highlighting TGFbeta signaling as a potential therapeutic target. |
