Mechanisms of action of retinal microglia in diabetic retinopathy (Review).
Level 5 - mechanism / opinion, no new human data
Narrative review of biological mechanisms and preclinical models without original human data
PubMed 40999978 · doi:10.3892/ijmm.2025.5643
What was done
This narrative review synthesized current literature on the dual physiological and pathological roles of retinal microglia in diabetic retinopathy pathogenesis, focusing on cellular polarization, inflammatory signaling pathways, and intercellular interactions.
What was found
No quantitative data, sample sizes, or statistical metrics were reported in the abstract. The review conceptually outlined that under physiological conditions, microglia maintain blood-retinal barrier integrity via debris phagocytosis and neurotrophic factor secretion. Hyperglycemia triggers pathological M1 polarization, inducing TNF-α and IL-1β secretion through the TLR4/MyD88/NF-κB axis, which acts alongside proangiogenic factors (VEGF, IGF-1) and glial networks (astrocytes and Müller cells) to accelerate blood-retinal barrier breakdown and neurovascular unit dysfunction.
Why it matters
It highlights microglial phenotypic modulation (such as promoting M2 anti-inflammatory shifts) and inflammatory signaling inhibition as potential multitarget strategies to overcome limitations of single-target diabetic retinopathy therapies.
Limits
As a narrative review, it presents mechanistic models and preclinical concepts rather than original empirical data, quantitative synthesis, or human clinical trial results.
Cited by
- supports Elevated blood sugar and systemic inflammation polarize microglia to an M1 phenotype that cannot phagocytize.