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Research Paper

Exosomes derived from BDNF-expressing 293T attenuate ischemic retinal injury in vitro and in vivo

Bojing Yan1, Lixin Gao1, Yingxiang Huang1, Xiaolei Wang1, Xuqiang Lang1, Fancheng Yan1, Bo Meng1, Xiaowei Sun2, Genlin Li3, Yanling Wang1
  • 1Department of Opthalmology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
  • 2Department of Ophthalmology, Yantai Yuhuangding Hospital Affiliated to Medical College of Qingdao University, Qingdao 264000, China
  • 3Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology and Visual Sciences Key Lab, Beijing 100730, China
Received: March 11, 2020Accepted: June 4, 2020Published: November 29, 2020
https://doi.org/10.18632/aging.202245

Copyright: © 2021 Yan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Retinal ischemia emerges in many ocular diseases and is a leading cause of neuronal death and dysfunction, resulting in irreversible visual impairment. We previously reported that brain-derived neurotrophic factor (BDNF)-expressing human 293T cells could steadily express BDNF and play a protective role in ARPE-19 cells, a human retinal epithelial cell line. Thus, we hypothesized that exosomes might be essential in the interaction between BDNF-expressing 293T cells and recipient cells. The study investigated whether exosomes derived from BDNF-expressing 293T cells (293T-Exo) can be internalized by ischemic retinal cells and exert neuroprotective roles. The results demonstrated that 293T-Exo significantly attenuated the loss of cell proliferation and cell death in R28 cells in response to oxygen-glucose deprivation treatment. Mechanistic studies revealed that the endocytosis of 293T-Exo by R28 cells displayed dose- and temperature-dependent patterns and may be mediated by the caveolar endocytic pathway via the integrin receptor. In the retinal ischemia rat model, the administration of 293T-Exo into the vitreous humor of ischemic eyes reduced apoptosis in the retina. Furthermore, 293T-Exo was mainly taken up by retinal neurons and retinal ganglion cells. Together, the results demonstrated that 293T-Exo has a neuroprotective effect in retinal ischemia and has therapeutic potential for retinal disorders.