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Aging: anti-miRs against miR-142-3p reduces angiogenesis and microglia activation

05-24-2021

Aging recently published "Intravitreal injection of anti-miRs against miR-142-3p reduces angiogenesis and microglia activation in a mouse model of laser- induced choroidal neovascularization" which reported that MiR-142-3p was overexpressed in murine CNV lesions and its pharmacological inhibition decreased vascular and microglia densities by 46% and 30%, respectively.

Consistently, miR-142-3p overexpression with mimics resulted in an increase of 136% and 126% of blood vessels and microglia recruitment.

Interestingly, miR-142-3p expression was linked to the activation state of mouse microglia cells as determined by morphological analysis through a computational method.

In vitro, miR-142-3p overexpression in human microglia cells modulated microglia activation, as shown by CD68 levels.

Together, these www.Aging-US.com data strongly support the unprecedented importance of miR-142- 3p-dependent vascular-inflammation axis during CNV progression, through microglia activation.

"These www.Aging-US.com data strongly support the unprecedented importance of miR-142- 3p-dependent vascular-inflammation axis during CNV progression, through microglia activation"

Dr. Agnès Noël from The University of Liège said, "Globally, 2.2 billion people suffer of vision impairment or blindness."

Although less frequent than atrophic age-related macular degeneration (AMD), neovascular AMD represents the most vision-threatening form of the disease.

At the experimental level, rodent models of laser-induced CNV are the most broadly used for neovascular AMD pre-clinical research.

Antibody-based anti- VEGF therapy is still the golden standard for the management of neovascular AMD.

Figure 4. MiR-142-3p influences microglia cell activation state in vivo. (A) Characterization of microglia morphology via cell solidity. The solidity of an object is defined as the ratio between its volume and its convex volume. Resting microglia are highly ramified while activated microglia present an amoeboid shape, with no or small ramifications. Activated microglia are characterized by a higher solidity. (B) CNV lesion area of flat-mounted retinas and surrounding healthy tissue were imaged at the 20X magnification and then processed and quantified. (C) Representative raw images and corresponding labelled images of resting and activated microglia area. (D) Microglia activity measured around the CNV lesion in mice injected with either miR-142-3p inhibitor or mimic and relative controls (n = 5-10 per experimental group). All results are presented as mean +- SEM. Mann Whitney test (* = p ≤ 0.05; ** = p ≤ 0.01).

However, only a few of these studies addressed the question of a functional role of microRNAs in AMD.

Through their capacity to regulate biological processes such as angiogenesis and inflammation, a functional contribution of miRNA in AMD is expected, but poorly documented.

The Noël Research Team concluded in their Aging Research Output, "miR-142-3p may exacerbate CNV by enhancing microglia migration and activation, and 574-3p, its downregulation in the CNV model did not Concerning miR-prompt us to consider it for an inhibition strategy therefore is worth considering as a potential therapeutic target in AMD.”

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DOI - https://doi.org/10.18632/aging.203035

Full Text - https://www.aging-us.com/article/203035/text

Correspondence to: Agnès Noël email: Agnes.Noel@uliege.be

Keywords: miR-142-3p, age-related macular degeneration, angiogenesis, inflammation, microglia

About Aging-US:

The mission of the journal is to understand the mechanisms surrounding aging and age-related diseases, including cancer as the main cause of death in the modern aged population.

The journal aims to promote 1) treatment of age-related diseases by slowing down aging, 2) validation of anti-aging drugs by treating age-related diseases, and 3) prevention of cancer by inhibiting aging. (Cancer and COVID-19 are age-related diseases.)

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