PMID- 32733897 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200928 IS - 2296-634X (Print) IS - 2296-634X (Electronic) IS - 2296-634X (Linking) VI - 8 DP - 2020 TI - Pre-treatment With Ranibizumab Aggravates PDT Injury and Alleviates Inflammatory Response in Choroid-Retinal Endothelial Cells. PG - 608 LID - 10.3389/fcell.2020.00608 [doi] LID - 608 AB - Polypoidal choroidal vasculopathy (PCV) is the predominant subtype of exudative age-related macular degeneration in Asians. Although photodynamic therapy (PDT) is widely used for PCV treatment, its long-term beneficial effects are unsatisfactory. Accumulating clinical investigations suggest that combined therapy with anti-vascular endothelial growth factor (anti-VEGF) and PDT is superior to PDT monotherapy. However, the optimal time of anti-VEGF before or after PDT remains controversial, hence it needs to further explore the mechanism underlying combined therapy. PDT causes selective damage to endothelial cells, which determines its angio-occlusive efficiency, yet the impact of anti-VEGF on PDT-induced endothelial injury is unclear. Here, we found that pre- compared to post-treatment with anti-VEGF ranibizumab (rani) significantly aggravates PDT injury in the rhesus macaque choroid-retinal endothelial (RF/6A) cell line. PDT activates apoptosis, necroptosis and NLRP3 inflammasome in RF/6A cells. Pre-treatment with rani promotes PDT-caused apoptosis via triggering caspase 8-mediated extrinsic apoptosis, and caspase 8 might also play a pivotal role in the rani's function of suppressing PDT-induced necroptosis and NLRP3 inflammasome activation. Our results implicate that pre-treatment with rani may enhance the angio-occlusive efficiency of PDT and alleviate endothelial inflammatory response, which gives it a great advantage over post-treatment. CI - Copyright (c) 2020 Liu, Zhu, Gong, Wang, Li and Xu. FAU - Liu, Yang AU - Liu Y AD - Shanghai Key Laboratory of Visual Impairment and Restoration, Eye & ENT Hospital, Fudan University, Shanghai, China. AD - NHC Key Laboratory of Myopia (Fudan University), Key Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, China. FAU - Zhu, Min AU - Zhu M AD - Shanghai Key Laboratory of Visual Impairment and Restoration, Eye & ENT Hospital, Fudan University, Shanghai, China. AD - NHC Key Laboratory of Myopia (Fudan University), Key Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, China. FAU - Gong, Ruowen AU - Gong R AD - Shanghai Key Laboratory of Visual Impairment and Restoration, Eye & ENT Hospital, Fudan University, Shanghai, China. AD - NHC Key Laboratory of Myopia (Fudan University), Key Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, China. FAU - Wang, Xin AU - Wang X AD - Shanghai Key Laboratory of Visual Impairment and Restoration, Eye & ENT Hospital, Fudan University, Shanghai, China. AD - NHC Key Laboratory of Myopia (Fudan University), Key Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, China. FAU - Li, Lei AU - Li L AD - Shanghai Key Laboratory of Visual Impairment and Restoration, Eye & ENT Hospital, Fudan University, Shanghai, China. AD - NHC Key Laboratory of Myopia (Fudan University), Key Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, China. FAU - Xu, Gezhi AU - Xu G AD - Shanghai Key Laboratory of Visual Impairment and Restoration, Eye & ENT Hospital, Fudan University, Shanghai, China. AD - NHC Key Laboratory of Myopia (Fudan University), Key Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, China. LA - eng PT - Journal Article DEP - 20200709 PL - Switzerland TA - Front Cell Dev Biol JT - Frontiers in cell and developmental biology JID - 101630250 PMC - PMC7363772 OTO - NOTNLM OT - NLRP3/IL-1beta inflammatory response OT - PDT OT - anti-VEGF OT - necroptosis OT - pre-treatment EDAT- 2020/08/01 06:00 MHDA- 2020/08/01 06:01 PMCR- 2020/01/01 CRDT- 2020/08/01 06:00 PHST- 2020/03/24 00:00 [received] PHST- 2020/06/19 00:00 [accepted] PHST- 2020/08/01 06:00 [entrez] PHST- 2020/08/01 06:00 [pubmed] PHST- 2020/08/01 06:01 [medline] PHST- 2020/01/01 00:00 [pmc-release] AID - 10.3389/fcell.2020.00608 [doi] PST - epublish SO - Front Cell Dev Biol. 2020 Jul 9;8:608. doi: 10.3389/fcell.2020.00608. eCollection 2020.