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Generation of Human Microglia to Combine Them with Retinal Organoids for Improved Disease Modeling
Published on: July 26, 2024
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Single-cell transcriptome analyses reveal microglia types associated with proliferative retinopathy.
Zhiping Liu1,2, Huidong Shi3,4, Jiean Xu1
1Vascular Biology Center, Medical College of Georgia, Augusta University, Augusta, Georgia, USA.
JCI Insight
|October 20, 2022
Summary
Researchers identified novel proangiogenic microglia subsets driving pathological angiogenesis in proliferative retinopathy (PR). These unique microglia promote retinal neovascularization, offering new therapeutic targets for blindness-causing eye diseases.
Area of Science:
- Ophthalmology
- Immunology
- Cell Biology
Background:
- Pathological angiogenesis causes irreversible blindness in proliferative retinopathy (PR).
- Mononuclear phagocytes (MPs) in neovascular areas contribute to aberrant retinal angiogenesis.
- The cellular heterogeneity of MPs makes it difficult to define specific roles in PR.
Purpose of the Study:
- Investigate microglia heterogeneity in neovascularization.
- Characterize transcriptional profiles and metabolic pathways of proangiogenic microglia.
- Utilize a mouse model of oxygen-induced PR (OIR).
Main Methods:
- Transcriptional single-cell sorting to map microglia populations.
- Analysis of microglia in room air (RA) and OIR mouse retinas.
- Immunohistochemistry (IHC) staining to identify PRAM location.
Main Results:
- Unveiled unique PR-associated microglia (PRAM) types.
- Identified markers, signaling pathways, and regulons for PRAM.
- Discovered proliferative and hypermetabolic microglia subsets expressing glycolytic enzymes and proangiogenic Igf1.
Conclusions:
- PRAM are spatially located within or around neovascular tufts.
- These microglia subsets have the potential to promote retinal angiogenesis.
- Findings have implications for treating PR and other pathological ocular angiogenesis diseases.
