PMID- 29675371 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20201001 IS - 2222-3959 (Print) IS - 2227-4898 (Electronic) IS - 2222-3959 (Linking) VI - 11 IP - 4 DP - 2018 TI - Mesenchymal stem cells-derived exosomes ameliorate blue light stimulation in retinal pigment epithelium cells and retinal laser injury by VEGF-dependent mechanism. PG - 559-566 LID - 10.18240/ijo.2018.04.04 [doi] AB - AIM: To observe the effect of exosomes derived from human umbilical cord blood mesenchymal stem cells (hUCMSCs) on the expression of vascular endothelial growth factor-A (VEGF-A) in blue light injured human retinal pigment epithelial (RPE) cells and laser-induced choroidal neovascularization (CNV) in rats. METHODS: Exosomes were isolated from hUCMSCs and characterized by transmission electron microscope and Western blot. MSCs-derived exosomes were cultured with RPE cells exposed to blue light. The mRNA and protein expression of VEGF-A were determined by real time-polymerase chain reaction (PCR) and Western blot, respectively. Immunofluorescence assay was used for the detection of the expression level of VEGF-A. We injected different doses of MSCs-derived exosomes intravitreally to observe and compare their effects in a mouse model of laser-induced retinal injury. The histological structure of CNV in rats was inspected by hematoxylin-eosin (HE) staining and fundus fluorescein angiography. The expression of VEGF-A was detected by immunohistochemistry. RESULTS: Exosomes exhibited the typical characteristic morphology (cup-shaped) and size (diameter between 50 and 150 nm). The exosomes marker, CD63, and hUCMSCs marker, CD90, showed a robust presence. In vitro, MSCs-derived exosomes downregulated the mRNA(Exo-L: t=6.485, 7.959, 9.286; Exo-M: t=7.517, 10.170, 13.413; Exo-H: t=10.317, 12.234, 14.592, P<0.05) and protein (Exo-L: t=2.945, 4.477, 6.657; Exo-M: t=4.713, 6.421, 8.836; Exo-H: t=6.539, 12.194, 12.783; P<0.05) expression of VEGF-A in RPE cells after blue light stimulation. In vivo, we found that the MSCs-derived exosomes reduced damage, distinctly downregulated VEGF-A (Exo-H: t=0.957, 1.382; P<0.05), and gradually improved the histological structures of CNV for a better visual function (Exo-L: 0.346, Exo-M: 3.382, Exo-H: 8.571; P<0.05). CONCLUSION: MSCs-derived exosomes ameliorate blue light stimulation in RPE cells and laser-induced retinal injury via downregulation of VEGF-A. FAU - He, Guang-Hui AU - He GH AD - Tianjin Eye Hospital; Tianjin Key Lab of Ophthalmology and Visual Science; Tianjin Eye Institute; Clinical College of Ophthalmology, Tianjin Medical University, Tianjin 300020, China. FAU - Zhang, Wei AU - Zhang W AD - Tianjin Eye Hospital; Tianjin Key Lab of Ophthalmology and Visual Science; Tianjin Eye Institute; Clinical College of Ophthalmology, Tianjin Medical University, Tianjin 300020, China. FAU - Ma, Ying-Xue AU - Ma YX AD - Tianjin Eye Hospital; Tianjin Key Lab of Ophthalmology and Visual Science; Tianjin Eye Institute; Clinical College of Ophthalmology, Tianjin Medical University, Tianjin 300020, China. FAU - Yang, Jing AU - Yang J AD - Tianjin Eye Hospital; Tianjin Key Lab of Ophthalmology and Visual Science; Tianjin Eye Institute; Clinical College of Ophthalmology, Tianjin Medical University, Tianjin 300020, China. FAU - Chen, Li AU - Chen L AD - Tianjin Eye Hospital; Tianjin Key Lab of Ophthalmology and Visual Science; Tianjin Eye Institute; Clinical College of Ophthalmology, Tianjin Medical University, Tianjin 300020, China. FAU - Song, Jian AU - Song J AD - Tianjin Eye Hospital; Tianjin Key Lab of Ophthalmology and Visual Science; Tianjin Eye Institute; Clinical College of Ophthalmology, Tianjin Medical University, Tianjin 300020, China. FAU - Chen, Song AU - Chen S AD - Tianjin Eye Hospital; Tianjin Key Lab of Ophthalmology and Visual Science; Tianjin Eye Institute; Clinical College of Ophthalmology, Tianjin Medical University, Tianjin 300020, China. LA - eng PT - Journal Article DEP - 20180418 PL - China TA - Int J Ophthalmol JT - International journal of ophthalmology JID - 101553860 PMC - PMC5902357 OTO - NOTNLM OT - choroidal neovascularization OT - exosome OT - human umbilical cord mesenchymal stem cell OT - retinal pigment epithelial cell OT - vascular endothelial growth factor EDAT- 2018/04/21 06:00 MHDA- 2018/04/21 06:01 PMCR- 2018/04/18 CRDT- 2018/04/21 06:00 PHST- 2017/08/04 00:00 [received] PHST- 2018/02/07 00:00 [accepted] PHST- 2018/04/21 06:00 [entrez] PHST- 2018/04/21 06:00 [pubmed] PHST- 2018/04/21 06:01 [medline] PHST- 2018/04/18 00:00 [pmc-release] AID - ijo-11-04-559 [pii] AID - 10.18240/ijo.2018.04.04 [doi] PST - epublish SO - Int J Ophthalmol. 2018 Apr 18;11(4):559-566. doi: 10.18240/ijo.2018.04.04. eCollection 2018.