Macrophage/microglia polarization for the treatment of diabetic retinopathy

Abstract

Macrophages/microglia are immune system defense and homeostatic cells that develop from bone marrow progenitor cells. According to the different phenotypes and immune responses of macrophages (Th1 and Th2), the two primary categories of polarized macrophages/microglia are those conventionally activated (M1) and alternatively activated (M2). Macrophage/microglial polarization is a key regulating factor in the development of inflammatory disorders, cancers, metabolic disturbances, and neural degeneration. Macrophage/microglial polarization is involved in inflammation, oxidative stress, pathological angiogenesis, and tissue healing processes in ocular diseases, particularly in diabetic retinopathy (DR). The functional phenotypes of macrophages/microglia affect disease progression and prognosis, and thus regulate the polarization or functional phenotype of microglia at different DR stages, which may offer new concepts for individualized therapy of DR. This review summarizes the involvement of macrophage/microglia polarization in physiological situations and in the pathological process of DR, and discusses the promising role of polarization in personalized treatment of DR.

Role of microglia/macrophage polarisation in intraocular diseases (Review)

“…The levels of iNOS (an M1 marker) and Arg-1 (an M2 marker) were higher in the retinas of db/db mice at five weeks of age. However, at eight weeks of age, iNOS levels continue to increase, whereas Arg-1 levels return to baseline ( 166 ).…”

Redox Regulation of Immunometabolism in Microglia Underpinning Diabetic Retinopathy

“…Under physiological circumstances, these pro-inflammatory mediators help remove toxic aggregated proteins and cellular debris from the retina. However, in the case of pathological conditions such as DR, overactivated M1-type microglia release large amounts of neurotoxic inflammatory factors (TNF-α, IL-1α, IL-1β, IL-6, NO, hydrogen peroxide, superoxide anion, and glutamate), and these pro-inflammatory factors induce leukocyte infiltration into the retinal vasculature, leading to vascular inflammation and disruption of the blood retinal barrier (BRB) [37,38]. Early BRB breakdown is a typical event in the early stage of DR, leading to increased exposure of microglia to extracellular signals.…”

Single‐cell RNA sequencing in exploring the pathogenesis of diabetic retinopathy

“…Previous studies has reported the microglia phenotypic switch in DR as from the alternative 'M2' (anti-inflammatory) state to the classical 'M1' (proinflammatory) state. 72 This simple dichotomous paradigm, however, is inadequate to fully describe the complicated biology of microglia activation in vivo. 73 The emergence and introduction of scRNA-seq have revolutionised the profiling of individual cells with high-throughput datasets, thereby achieving a more precise and multifaceted characterisation of microglia subpopulations in DR. 74 Activated microglia secrete various pro-inflammatory cytokines and chemokines that cause chronic inflammation.…”