An Integrative Multi-Omics Analysis Reveals MicroRNA-143 as a Potential Therapeutic to Attenuate Retinal Angiogenesis

Area of Science:

• Ophthalmology
• Molecular Biology
• Genetics

Background:

• Retinal neovascularization is a serious complication of proliferative diabetic retinopathy (PDR).
• MicroRNAs (miRNAs) regulate gene expression and are implicated in retinal neovascularization.
• The specific role of miR-143-3p in this process requires further elucidation.

Purpose of the Study:

• To investigate the role of miR-143-3p in retinal neovascularization.
• To determine the therapeutic potential of miR-143-3p in a rat model of oxygen-induced retinopathy (OIR).

Main Methods:

• miRNA-sequencing was used to analyze miRNA expression in OIR rat retinas.
• Synthetic miR-143 mimics were administered via intravitreal injection in OIR rats.
• Functional assays, multiomics analysis, and CIBERSORTx were employed to assess cellular mechanisms and patient samples.

Main Results:

• miR-143-3p was significantly downregulated in OIR rat retinas.
• Intravitreal miR-143 mimics reduced retinal neovascularization in OIR rats.
• miR-143-3p negatively impacts endothelial cell migration and tube formation by regulating cell-matrix adhesion and HIF-1 signaling, with thrombospondin 1 and plasminogen activator inhibitor identified as key targets in PDR patients.

Conclusions:

• miR-143-3p is downregulated in conditions leading to retinal neovascularization.
• Restoring miR-143-3p levels shows therapeutic promise for PDR by inhibiting endothelial cell activity and neovascularization.
• miR-143-3p is essential for limiting endothelial cell-matrix adhesion and suppressing retinal neovascularization.