PMID- 37774941 OWN - NLM STAT- MEDLINE DCOM- 20231216 LR - 20240131 IS - 1095-9319 (Electronic) IS - 0026-2862 (Linking) VI - 151 DP - 2024 Jan TI - Astrocytic expression of Yes-associated protein (YAP) regulates retinal neovascularization in a mouse model of oxygen-induced retinopathy. PG - 104611 LID - S0026-2862(23)00137-1 [pii] LID - 10.1016/j.mvr.2023.104611 [doi] AB - Pathological neovascularization is the hallmark of many vascular oculopathies. There is still a great deal of uncertainty surrounding retinal neovascularization research. A working hypothesis that astrocytic Yes-associated protein (YAP) act as a key factor in retinal neovascularization was proposed. And our study was conducted to verified this hypothesis. In vivo, we successfully generated mice deficient in YAP in astrocytes (YAP(f/f) GFAP-Cre mice) and set up oxygen-induced retinopathy (OIR) model. Pathological neovascularization was evaluated by immunofluorescence staining and western blotting. In vitro, cultured retinal astrocytes were transfected with YAP siRNA. Enzyme-linked immunosorbent assay (ELISA) and western blot were used to determine the proteins in the supernatants and cells. The results showed that YAP was upregulated and activated in the OIR mice retinas. Conditional ablation of YAP aggravated pathological neovascularization, along with the upregulation of vascular endothelial growth factor A (VEGF-A) and monocyte chemoattractant protein-1 (MCP-1). Studies in vitro confirmed that the knockdown of YAP in astrocytes lead to increases in VEGF-A and MCP-1 levels, thus enhancing pro-angiogenic capability of YAP-deficit astrocytes. In conclusion, astrocytic YAP alleviates retinal pathological angiogenesis by inhibiting the over-activation of astrocytes, which suppresses excessive VEGF-A production and neuroinflammation. CI - Copyright (c) 2023. Published by Elsevier Inc. FAU - Liu, Zhifei AU - Liu Z AD - Department of Ophthalmology, Research Institute of Surgery & Daping Hospital, Army Medical Center of PLA, Army Medical University, Chongqing, China. FAU - Zhang, Jieqiong AU - Zhang J AD - Department of Ophthalmology, Research Institute of Surgery & Daping Hospital, Army Medical Center of PLA, Army Medical University, Chongqing, China. FAU - Li, Xue AU - Li X AD - Department of Ophthalmology, Research Institute of Surgery & Daping Hospital, Army Medical Center of PLA, Army Medical University, Chongqing, China. FAU - Hu, Qiumei AU - Hu Q AD - Department of Ophthalmology, Research Institute of Surgery & Daping Hospital, Army Medical Center of PLA, Army Medical University, Chongqing, China. FAU - Chen, Xi AU - Chen X AD - Department of Ophthalmology, Research Institute of Surgery & Daping Hospital, Army Medical Center of PLA, Army Medical University, Chongqing, China. FAU - Luo, Linlin AU - Luo L AD - Department of Ophthalmology, Research Institute of Surgery & Daping Hospital, Army Medical Center of PLA, Army Medical University, Chongqing, China. FAU - Ai, Liqianyu AU - Ai L AD - Department of Ophthalmology, Research Institute of Surgery & Daping Hospital, Army Medical Center of PLA, Army Medical University, Chongqing, China. Electronic address: echoqian@tmmu.edu.cn. FAU - Ye, Jian AU - Ye J AD - Department of Ophthalmology, Research Institute of Surgery & Daping Hospital, Army Medical Center of PLA, Army Medical University, Chongqing, China. Electronic address: yejian1979@tmmu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230928 PL - United States TA - Microvasc Res JT - Microvascular research JID - 0165035 RN - S88TT14065 (Oxygen) RN - 0 (Vascular Endothelial Growth Factor A) RN - 0 (YAP-Signaling Proteins) SB - IM MH - Animals MH - Mice MH - *Retinal Neovascularization/metabolism MH - Oxygen/toxicity/metabolism MH - Vascular Endothelial Growth Factor A/metabolism MH - Neovascularization, Pathologic/metabolism MH - YAP-Signaling Proteins MH - Astrocytes/pathology MH - Mice, Inbred C57BL MH - Disease Models, Animal MH - Animals, Newborn OTO - NOTNLM OT - Astrocytes OT - Neovascularization OT - Oxygen-induced retinopathy OT - YAP COIS- Declaration of competing interest The authors declare that they have no competing interests. EDAT- 2023/09/30 09:42 MHDA- 2023/12/17 09:43 CRDT- 2023/09/29 19:16 PHST- 2023/03/29 00:00 [received] PHST- 2023/09/19 00:00 [revised] PHST- 2023/09/19 00:00 [accepted] PHST- 2023/12/17 09:43 [medline] PHST- 2023/09/30 09:42 [pubmed] PHST- 2023/09/29 19:16 [entrez] AID - S0026-2862(23)00137-1 [pii] AID - 10.1016/j.mvr.2023.104611 [doi] PST - ppublish SO - Microvasc Res. 2024 Jan;151:104611. doi: 10.1016/j.mvr.2023.104611. Epub 2023 Sep 28.