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Updated: Apr 28, 2026
Isolation of Primary Mouse Retinal Glial Müller Cells
Published on: August 30, 2024
Reactive microglia and macrophage facilitate the formation of Müller glia-derived retinal progenitors
Andy J Fischer1, Christopher Zelinka, Donika Gallina
1Department of Neuroscience, College of Medicine, The Ohio State University, Columbus, Ohio.
Abstract:
In retinas where Müller glia have been stimulated to become progenitor cells, reactive microglia are always present. Thus, we investigated how the activation or ablation of microglia/macrophage influences the formation of Müller glia-derived progenitor cells (MGPCs) in the retina in vivo. Intraocular injections of the Interleukin-6 (IL6) stimulated the reactivity of microglia/macrophage, whereas other types of retinal glia appear largely unaffected. In acutely damaged retinas where all of the retinal microglia/macrophage were ablated, the formation of proliferating MGPCs was greatly diminished. With the microglia ablated in damaged retinas, levels of Notch and related genes were unchanged or increased, whereas levels of ascl1a, TNFα, IL1β, complement component 3 (C3) and C3a receptor were significantly reduced. In the absence of retinal damage, the combination of insulin and Fibroblast growth factor 2 (FGF2) failed to stimulate the formation of MGPCs when the microglia/macrophage were ablated. In addition, intraocular injections of IL6 and FGF2 stimulated the formation of MGPCs in the absence of retinal damage, and this generation of MGPCs was blocked when the microglia/macrophage were absent. We conclude that the activation of microglia and/or infiltrating macrophage contributes to the formation of proliferating MGPCs, and these effects may be mediated by components of the complement system and inflammatory cytokines.
Insights
Microglia and macrophages are crucial for forming Müller glia-derived progenitor cells (MGPCs) in the retina. Their activation, influenced by Interleukin-6 (IL6), promotes MGPC proliferation, potentially via complement system components and inflammatory cytokines.
Area of Science:
- Neuroscience
- Retinal Biology
- Cellular Biology
Background:
- Reactive microglia are consistently observed when Müller glia are stimulated to form progenitor cells.
- The role of microglia/macrophage activation in this process remains unclear.
Purpose of the Study:
- To investigate how microglia/macrophage activation or ablation influences Müller glia-derived progenitor cell (MGPC) formation in vivo.
- To elucidate the mechanisms by which microglia/macrophages contribute to retinal regeneration.
Main Methods:
- Intraocular injections of Interleukin-6 (IL6) to stimulate microglia/macrophage reactivity.
- Ablation of retinal microglia/macrophage in acutely damaged and undamaged retinas.
- Assessment of MGPC proliferation and gene expression (Notch, ascl1a, TNFα, IL1β, C3, C3a receptor).
- Stimulation of MGPC formation using insulin and Fibroblast growth factor 2 (FGF2) with and without microglia/macrophage presence.
Main Results:
- Ablation of microglia/macrophage in damaged retinas significantly reduced proliferating MGPC formation.
- Microglia ablation led to decreased levels of ascl1a, TNFα, IL1β, C3, and C3a receptor, while Notch and related genes remained unchanged or increased.
- In undamaged retinas, microglia/macrophage ablation blocked MGPC formation induced by IL6 and FGF2.
- IL6 and FGF2 stimulated MGPC formation in undamaged retinas, an effect dependent on microglia/macrophage presence.
Conclusions:
- Microglia and/or infiltrating macrophage activation are essential for the formation of proliferating MGPCs.
- The complement system and inflammatory cytokines may mediate the pro-regenerative effects of microglia/macrophages.
- Targeting microglia/macrophage activation could be a therapeutic strategy for retinal repair.
