PMID- 36229856 OWN - NLM STAT- MEDLINE DCOM- 20221017 LR - 20221222 IS - 1478-811X (Electronic) IS - 1478-811X (Linking) VI - 20 IP - 1 DP - 2022 Oct 13 TI - PGE(2) promotes macrophage recruitment and neovascularization in murine wet-type AMD models. PG - 155 LID - 10.1186/s12964-022-00973-6 [doi] LID - 155 AB - Age-related macular degeneration (AMD), a progressive chronic disease of the central retina, is a leading cause of blindness worldwide. Activated macrophages recruited to the injured eyes greatly contribute to the pathogenesis of choroidal neovascularization (CNV) in exudative AMD (wet AMD). This study describes the effects of cyclooxygenase-2 (COX2)/prostaglandin E(2) (PGE(2)) signalling on the macrophage activation and CNV formation of wet AMD. In a mouse model of laser-induced wet AMD, the mice received an intravitreal injection of celecoxib (a selective COX2 inhibitor). Optical coherence tomography (OCT), fundus fluorescein angiography (FFA), choroidal histology of the CNV lesions, and biochemical markers were assessed. The level of PGE(2) expression was high in the laser-induced CNV lesions. Macrophage recruitment and CNV development were significantly less after celecoxib treatment. E-prostanoid1 receptor (EP(1)R)/protein kinase C (PKC) signalling was involved in M2 macrophage activation and interleukin-10 (IL-10) production of bone marrow-derived macrophages (BMDMs) in vitro. In addition, IL-10 was found to induce the proliferation and migration of human choroidal microvascular endothelial cells (HCECs). Thus, the PGE(2)/EP(1)R signalling network serves as a potential therapeutic target for CNV of the wet-type AMD. Video abstract. CI - (c) 2022. The Author(s). FAU - Zhan, Pengfei AU - Zhan P AD - Department of Ophthalmology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, 299 Qingyang Road, Wuxi, 214023, Jiangsu, People's Republic of China. FAU - Cui, Yuqing AU - Cui Y AD - Department of Ophthalmology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, 299 Qingyang Road, Wuxi, 214023, Jiangsu, People's Republic of China. FAU - Cao, Yujuan AU - Cao Y AD - Department of Ophthalmology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, 299 Qingyang Road, Wuxi, 214023, Jiangsu, People's Republic of China. AD - Center of Clinical Research, The Affiliated Wuxi People's Hospital of Nanjing Medical University, 299 Qingyang Road, Wuxi, 214023, Jiangsu, People's Republic of China. AD - Department of Ophthalmology, The Affiliated Wuxi No.2 People's Hospital of Nanjing Medical University, Wuxi, 214023, Jiangsu, People's Republic of China. FAU - Bao, Xun AU - Bao X AD - Department of Ophthalmology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, 299 Qingyang Road, Wuxi, 214023, Jiangsu, People's Republic of China. FAU - Wu, Meili AU - Wu M AD - Center of Clinical Research, The Affiliated Wuxi People's Hospital of Nanjing Medical University, 299 Qingyang Road, Wuxi, 214023, Jiangsu, People's Republic of China. FAU - Yang, Qian AU - Yang Q AD - Department of Ophthalmology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, 299 Qingyang Road, Wuxi, 214023, Jiangsu, People's Republic of China. FAU - Yang, Jiahui AU - Yang J AD - Department of Ophthalmology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, 299 Qingyang Road, Wuxi, 214023, Jiangsu, People's Republic of China. FAU - Zheng, Haohan AU - Zheng H AD - Department of Ophthalmology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, 299 Qingyang Road, Wuxi, 214023, Jiangsu, People's Republic of China. FAU - Zou, Jian AU - Zou J AD - Center of Clinical Research, The Affiliated Wuxi People's Hospital of Nanjing Medical University, 299 Qingyang Road, Wuxi, 214023, Jiangsu, People's Republic of China. FAU - Xie, Tianhua AU - Xie T AD - Department of Ophthalmology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, 299 Qingyang Road, Wuxi, 214023, Jiangsu, People's Republic of China. FAU - Cai, Jiping AU - Cai J AD - Department of Ophthalmology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, 299 Qingyang Road, Wuxi, 214023, Jiangsu, People's Republic of China. FAU - Yao, Yong AU - Yao Y AUID- ORCID: 0000-0002-5506-7101 AD - Department of Ophthalmology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, 299 Qingyang Road, Wuxi, 214023, Jiangsu, People's Republic of China. yongyao@njmu.edu.cn. AD - Department of Ophthalmology, The Affiliated Wuxi No.2 People's Hospital of Nanjing Medical University, Wuxi, 214023, Jiangsu, People's Republic of China. yongyao@njmu.edu.cn. FAU - Wang, Xiaolu AU - Wang X AD - Center of Clinical Research, The Affiliated Wuxi People's Hospital of Nanjing Medical University, 299 Qingyang Road, Wuxi, 214023, Jiangsu, People's Republic of China. xlwang@njmu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Video-Audio Media DEP - 20221013 PL - England TA - Cell Commun Signal JT - Cell communication and signaling : CCS JID - 101170464 RN - 0 (Cyclooxygenase 2 Inhibitors) RN - 130068-27-8 (Interleukin-10) RN - EC 1.14.99.1 (Cyclooxygenase 2) RN - EC 2.7.11.13 (Protein Kinase C) RN - JCX84Q7J1L (Celecoxib) RN - K7Q1JQR04M (Dinoprostone) SB - IM MH - Animals MH - Celecoxib/pharmacology MH - *Choroidal Neovascularization/etiology MH - Cyclooxygenase 2/metabolism MH - Cyclooxygenase 2 Inhibitors/metabolism/therapeutic use MH - Dinoprostone/metabolism MH - Endothelial Cells/metabolism MH - Humans MH - *Interleukin-10/metabolism MH - Macrophages/metabolism MH - Mice MH - Protein Kinase C/metabolism PMC - PMC9558420 OTO - NOTNLM OT - AMD OT - Macrophage OT - Neovascularization OT - PGE2 COIS- The authors declare that there is no duality of interest associated with this manuscript. EDAT- 2022/10/14 06:00 MHDA- 2022/10/18 06:00 PMCR- 2022/10/13 CRDT- 2022/10/13 23:44 PHST- 2021/10/25 00:00 [received] PHST- 2022/09/18 00:00 [accepted] PHST- 2022/10/13 23:44 [entrez] PHST- 2022/10/14 06:00 [pubmed] PHST- 2022/10/18 06:00 [medline] PHST- 2022/10/13 00:00 [pmc-release] AID - 10.1186/s12964-022-00973-6 [pii] AID - 973 [pii] AID - 10.1186/s12964-022-00973-6 [doi] PST - epublish SO - Cell Commun Signal. 2022 Oct 13;20(1):155. doi: 10.1186/s12964-022-00973-6.