Macrophage microRNA-150 promotes pathological angiogenesis as seen in age-related macular degeneration

Abstract

Macrophage aging is pathogenic in diseases of the elderly, including age-related macular degeneration (AMD), a leading cause of blindness in older adults. However, the role of microRNAs, which modulate immune processes, in regulating macrophage dysfunction and thereby promoting age-associated diseases is underexplored. Here, we report that microRNA-150 (miR-150) coordinates transcriptomic changes in aged murine macrophages, especially those associated with aberrant lipid trafficking and metabolism in AMD pathogenesis. Molecular profiling confirmed that aged murine macrophages exhibit dysregulated ceramide and phospholipid profiles compared with young macrophages. Of translational relevance, upregulation of miR-150 in human peripheral blood mononuclear cells was also significantly associated with increased odds of AMD, even after controlling for age. Mechanistically, miR-150 directly targets stearoyl-CoA desaturase-2, which coordinates macrophage-mediated inflammation and pathologic angiogenesis, as seen in AMD, in a VEGF-independent manner. Together, our results implicate miR-150 as pathogenic in AMD and provide potentially novel molecular insights into diseases of aging.

Neutrophil-derived extracellular vesicles: proinflammatory trails and anti-inflammatory microvesicles

“…Moreover, miR-24-3p and miR-4454 are found in monocyte-derived dendritic cells (Fell et al, 2016) and alveolar macrophages (Armstrong et al, 2017). In contrast, miR-126-3p and miR-150-5p are expressed in M2 polarized macrophages (Cobos Jiménez et al, 2014; Escate et al, 2016) and are associated with suppression of inflammation (Harris et al, 2008; Lin et al, 2018; Manoharan et al, 2014; Shantikumar et al, 2012). Our results showed differential miRNA expression in NDTRs and NDMVs; thus, neutrophils incorporate different types of miRNAs into EVs according to the immune environments.…”

MiR‐505 promotes M2 polarization in choroidal neovascularization model mice by targeting transmembrane protein 229B

“…miR‐184 was found to be able to regulate ezrin, LAMP‐1 expression, affected phagocytosis in human retinal pigment epithelium and was significantly downregulated in AMD . Mechanically, macrophage miR‐150 was proposed to promote pathological angiogenesis featured in AMD . So far, the potential contribution in the pathology of AMD was not yet addressed.…”

“…25 Mechanically, macrophage miR-150 was proposed to promote pathological angiogenesis featured in AMD. 20 So far, the potential contribution in the pathology of AMD was not yet addressed. In this study, we have provided experimental evidences in support of the critical involvement of miR-505 in AMD.…”

“…Post‐mortem retinal tissues from wet AMD patients were obtained from the archived tissue bank and used in strict accordance with the protocol approved by the Ethics Committee of the Affiliated Hospital of Guizhou Medical University (#AHGMU2018‐073U). The selection criteria were described previously with all patients classified as no AMD, early‐stage and wet AMD. Wet AMD was defined as CNV in at least one eye, and patients with other complications such as pattern dystrophy, macular telangiectasia, dominant drusen or central serous chorioretinopathy were excluded.…”

A Circulating MicroRNA Profile in a Laser-Induced Mouse Model of Choroidal Neovascularization

“…In total, six studies met these criteria [21][22][23][24][25][26]. Studies that investigated intracellular cmiRNAs [54,55], cmiRNAs in exosomes [56], a combination of nAMD and geographic atrophy AMD patients [57,58], and a combination of nAMD and congenital hemochromatosis patients [59] were excluded.…”