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Updated: Jun 2, 2026

Three-dimensional Confocal Analysis of Microglia/macrophage Markers of Polarization in Experimental Brain Injury
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Heterotypic macrophages/microglia differentially contribute to retinal ischaemia and neovascularisation

Muneo Yamaguchi1, Shintaro Nakao2,3,4,5, Mitsuru Arima1

  • 1Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Diabetologia
|July 8, 2024
PubMed
Abstract

Insights

Macrophages and microglia play distinct roles in diabetic retinopathy progression. Targeting these immune cells, particularly M1-like macrophages/microglia, may offer new therapeutic strategies for proliferative diabetic retinopathy.

Area of Science:

  • Ophthalmology
  • Immunology
  • Vascular Biology

Background:

  • Diabetic retinopathy (DR) involves neuroinflammation, leading to retinal ischemia and neovascularization.
  • Infiltrating macrophages and microglia are implicated in DR, but their specific roles are unclear.

Purpose of the Study:

  • To elucidate the distinct functions of macrophages and microglia in the pathogenesis of proliferative ischemic retinopathies.

Main Methods:

  • Utilized a murine oxygen-induced retinopathy model and clinical imaging (OCT, OCT angiography).
  • Assessed macrophage/microglia phenotypes using immunostaining, qRT-PCR, flow cytometry, and scRNA-seq.
  • Investigated the effects of Rho-kinase (ROCK) inhibition and other agents on macrophage infiltration and ischemia.

Main Results:

  • M1-like and M2-like macrophage/microglia markers were upregulated in ischemic areas and around neovessels.
  • scRNA-seq identified distinct ischemia-related macrophage/microglia clusters expressing M1 markers and CCR2.
  • ROCK inhibition reduced CCL2 expression and CCR2-positive M1-like cells; suppressing macrophage infiltration reduced retinal ischemia.

Conclusions:

  • Heterotypic macrophages/microglia differentially contribute to retinal ischemia and neovascularization in DR.
  • Findings suggest a basis for targeted, cell-specific therapies to prevent sight-threatening PDR.
Keywords:
Diabetic ischaemiaIschaemic retinopathyMacrophage polarisationMicrogliaMonocyte

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