Lens epithelial cell‐derived exosome inhibits angiogenesis in ocular pathological neovascularization through its delivery of miR‐146a‐5p

Abstract

Abnormal ocular neovascularization, a major pathology of eye diseases, leads to severe visual loss. The role of lens epithelial cell (LEC)‐derived exosomes (Lec‐exo) is largely unknown. Thus, we aimed to investigate whether Lec‐exo can inhibit abnormal ocular neovascularization and explore the possible mechanisms. In our study, we proved the first evidence that exosomes derived from LECs attenuated angiogenesis in both oxygen‐induced retinopathy and laser‐induced choroidal neovascularization mice models. Further in vitro experiments proved that Lec‐exo inhibited proliferation, migration, and tube formation capability of human umbilical vein endothelial cells in high glucose condition. Further high‐throughput miRNAs sequencing analysis detected that miR‐146a‐5p was enriched in Lec‐exo. Mechanistically, exosomal miR‐146a‐5p was delivered to endothelial cells and bound to the NRAS coding sequence, which subsequently inactivated AKT/ERK signaling pathway. We successfully elucidated the function of Lec‐exo in inhibiting abnormal ocular neovascularization, which may offer a promising strategy for treatment of abnormal ocular neovascularization.

Classical and Innovative Evidence for Therapeutic Strategies in Retinal Dysfunctions

“…On the other hand, some lncRNAs have protective effects, like TPTEP1, that reduces VEGFA expression and therefore neovascularization [139]. Another target heavily modulated by ncRNAs is the PI3K/Akt pathway [140][141][142][143][144], responsible for cell proliferation and tube formation potential.…”