Human lens epithelial-secreted exosomes attenuate ocular angiogenesis via inhibiting microglial activation

Exp Eye Res. 2024 Apr:241:109837. doi: 10.1016/j.exer.2024.109837. Epub 2024 Feb 20.

Abstract

The lens is an avascular tissue, where epithelial cells (LECs) are the primary living cells. The role of LECs-derived exosomes (LEC-exos) is largely unknown. In our study, we determined the anti-angiogenic role of LEC-exos, manifested as regressed retinal neovascularization (NV) using the oxygen-induced retinopathy (OIR), and reduced choroidal NV size and pathological vascular leakage using the laser-induced choroidal neovascularization (laser-induced CNV). Furthermore, the activation and accumulation of microglia were also restricted by LEC-exos. Based on Luminex multiplex assays, the expressions of chemokines such as SCYB16/CXCL16, MCP-1/CCL2, I-TAC/CXCL11, and MIP 3beta/CCL19 were decreased after treatment with LEC-exos. Transwell assays showed that LEC-exos restricted the migration of the mouse microglia cell line (BV2 cells). After incubation with LEC-exos-treated BV2 cells, human umbilical vein endothelial cells (hUVECs) were collected for further evaluation using tube formation, Transwell assays, and 5-ethynyl-2'-deoxyuridine (EDU) assays. Using in vitro experiments, the pro-angiogenic effect of microglia was restricted by LEC-exos. Hence, it was investigated that LEC-exos attenuated ocular NV, which might attribute to the inhibition of microglial activation and accumulation.

Keywords: Angiogenesis; Exosome; Lens epithelial cell; Microglia.

MeSH terms

  • Angiogenesis
  • Animals
  • Choroidal Neovascularization* / metabolism
  • Exosomes* / metabolism
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Mesenchymal Stem Cells*
  • Mice
  • Microglia
  • Neovascularization, Physiologic / physiology