{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T17:00:23Z","timestamp":1778864423131,"version":"3.51.4"},"reference-count":177,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2020,7,4]],"date-time":"2020-07-04T00:00:00Z","timestamp":1593820800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Vasculogenesis and angiogenesis play a crucial role in embryonic development. Pathological neovascularization in ocular tissues can lead to vision-threatening vascular diseases, including proliferative diabetic retinopathy, retinal vein occlusion, retinopathy of prematurity, choroidal neovascularization, and corneal neovascularization. Neovascularization involves various cellular processes and signaling pathways and is regulated by angiogenic factors such as vascular endothelial growth factor (VEGF) and hypoxia-inducible factor (HIF). Modulating these circuits may represent a promising strategy to treat ocular neovascular diseases. Lipid mediators derived from membrane lipids are abundantly present in most tissues and exert a wide range of biological functions by regulating various signaling pathways. In particular, glycerophospholipids, sphingolipids, and polyunsaturated fatty acids exert potent pro-angiogenic or anti-angiogenic effects, according to the findings of numerous preclinical and clinical studies. In this review, we summarize the current knowledge regarding the regulation of ocular neovascularization by lipid mediators and their metabolites. A better understanding of the effects of lipid signaling in neovascularization may provide novel therapeutic strategies to treat ocular neovascular diseases and other human disorders.<\/jats:p>","DOI":"10.3390\/ijms21134758","type":"journal-article","created":{"date-parts":[[2020,7,6]],"date-time":"2020-07-06T03:19:27Z","timestamp":1594005567000},"page":"4758","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Lipid Signaling in Ocular Neovascularization"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6182-4343","authenticated-orcid":false,"given":"Ryo","family":"Terao","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroki","family":"Kaneko","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1038\/nrm4080","article-title":"The systematic analysis of protein-lipid interactions comes of age","volume":"16","author":"Saliba","year":"2015","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.plipres.2013.12.001","article-title":"Regulation of energy metabolism by long-chain fatty acids","volume":"53","author":"Nakamura","year":"2014","journal-title":"Prog. Lipid Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"R381","DOI":"10.1016\/j.cub.2018.01.086","article-title":"Membranes and evolution","volume":"28","author":"Gould","year":"2018","journal-title":"Curr. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Casares, D., Escrib\u00e1, P.V., and Rossell\u00f3, C.A. (2019). Membrane Lipid Composition: Effect on Membrane and Organelle Structure, Function and Compartmentalization and Therapeutic Avenues. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20092167"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1038\/nrm.2017.138","article-title":"Understanding the diversity of membrane lipid composition","volume":"19","author":"Harayama","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.molmed.2005.11.004","article-title":"Membrane-lipid therapy: A new approach in molecular medicine","volume":"12","year":"2006","journal-title":"Trends Mol. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1097\/MOL.0000000000000334","article-title":"Intestinal phospholipid and lysophospholipid metabolism in cardiometabolic disease","volume":"27","author":"Hui","year":"2016","journal-title":"Curr. Opin. Lipidol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3671","DOI":"10.1111\/cas.13802","article-title":"The role of sphingosine-1-phosphate in inflammation and cancer progression","volume":"109","author":"Nagahashi","year":"2018","journal-title":"Cancer Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1007\/s10384-003-0059-2","article-title":"Differential regulation of focal adhesion kinase and paxillin phosphorylation by the small GTP-binding protein Rho in human corneal epithelial cells","volume":"48","author":"Saito","year":"2004","journal-title":"Jpn. J. Ophthalmol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Solati, Z., and Ravandi, A. (2019). Lipidomics of Bioactive Lipids in Acute Coronary Syndromes. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20051051"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1038\/nm1336","article-title":"Trans-arachidonic acids generated during nitrative stress induce a thrombospondin-1-dependent microvascular degeneration","volume":"11","author":"Sennlaub","year":"2005","journal-title":"Nat. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1124\/jpet.300.2.385","article-title":"Novel lipid mediator regulators of endothelial cell proliferation and migration: Aspirin-triggered-15R-lipoxin A(4) and lipoxin A(4)","volume":"300","author":"Fierro","year":"2002","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Moccia, F., Negri, S., Shekha, M., Faris, P., and Guerra, G. (2019). Endothelial Ca(2+) Signaling, Angiogenesis and Vasculogenesis: Just What It Takes to Make a Blood Vessel. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20163962"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"65","DOI":"10.3389\/fcvm.2017.00065","article-title":"Angiogenesis, Cancer, and Vascular Aging","volume":"4","author":"Moriya","year":"2017","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1159\/000448551","article-title":"Vasculogenesis and Its Cellular Therapeutic Applications","volume":"203","author":"Ratajska","year":"2017","journal-title":"Cells Tissues Organs"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.mvr.2007.04.011","article-title":"Retinal and choroidal microangiopathies: Therapeutic opportunities","volume":"74","author":"Afzal","year":"2007","journal-title":"Microvasc. Res."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Kim, J.Y., and Lee, J.Y. (2017). Targeting Tumor Adaption to Chronic Hypoxia: Implications for Drug Resistance, and How It Can Be Overcome. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18091854"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1038\/74651","article-title":"Mechanisms of angiogenesis and arteriogenesis","volume":"6","author":"Carmeliet","year":"2000","journal-title":"Nat. Med."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Rajabi, M., and Mousa, S.A. (2017). The Role of Angiogenesis in Cancer Treatment. Biomedicines, 5.","DOI":"10.3390\/biomedicines5020034"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1007\/s10456-017-9562-9","article-title":"Tumor angiogenesis and vascular normalization: Alternative therapeutic targets","volume":"20","author":"Viallard","year":"2017","journal-title":"Angiogenesis"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1038\/nature10144","article-title":"Molecular mechanisms and clinical applications of angiogenesis","volume":"473","author":"Carmeliet","year":"2011","journal-title":"Nature"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1002\/cphy.c160048","article-title":"Molecular Regulation of Sprouting Angiogenesis","volume":"8","author":"Duran","year":"2017","journal-title":"Compr. Physiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1016\/j.cmet.2013.08.001","article-title":"Role of endothelial cell metabolism in vessel sprouting","volume":"18","author":"Georgiadou","year":"2013","journal-title":"Cell Metab."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1038\/380435a0","article-title":"Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele","volume":"380","author":"Carmeliet","year":"1996","journal-title":"Nature"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1016\/j.cell.2019.01.021","article-title":"VEGF in Signaling and Disease: Beyond Discovery and Development","volume":"176","author":"Apte","year":"2019","journal-title":"Cell"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"151019","DOI":"10.1242\/dev.151019","article-title":"Vascular endothelial growth factor signaling in development and disease","volume":"145","author":"Karaman","year":"2018","journal-title":"Development"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1681\/ASN.2018080853","article-title":"Therapeutic Inhibition of VEGF Signaling and Associated Nephrotoxicities","volume":"30","author":"Estrada","year":"2019","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.canlet.2004.12.009","article-title":"Rho, Rac, Pak and angiogenesis: Old roles and newly identified responsibilities in endothelial cells","volume":"229","author":"Fryer","year":"2005","journal-title":"Cancer Lett."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1002\/med.21477","article-title":"Hypoxia-inducible factor-1 (HIF-1) inhibitors from the last decade (2007 to 2016): A \u201cstructure-activity relationship\u201d perspective","volume":"38","author":"Bhattarai","year":"2018","journal-title":"Med. Res. Rev."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"6735","DOI":"10.1158\/1078-0432.CCR-07-4843","article-title":"The interleukin-8 pathway in cancer","volume":"14","author":"Waugh","year":"2008","journal-title":"Clin. Cancer Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5014","DOI":"10.1091\/mbc.e07-01-0004","article-title":"Transactivation of vascular endothelial growth factor receptor-2 by interleukin-8 (IL-8\/CXCL8) is required for IL-8\/CXCL8-induced endothelial permeability","volume":"18","author":"Petreaca","year":"2007","journal-title":"Mol. Biol. Cell"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.tcm.2005.11.008","article-title":"Angiogenesis: The VE-cadherin switch","volume":"16","author":"Wallez","year":"2006","journal-title":"Trends Cardiovasc. Med."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Shim, J.W., and Madsen, J.R. (2018). VEGF Signaling in Neurological Disorders. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19010275"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1007\/s10456-016-9497-6","article-title":"Bone marrow-derived cells in ocular neovascularization: Contribution and mechanisms","volume":"19","author":"Gao","year":"2016","journal-title":"Angiogenesis"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4665","DOI":"10.1096\/fj.201700336R","article-title":"Animal models of ocular angiogenesis: From development to pathologies","volume":"31","author":"Liu","year":"2017","journal-title":"FASEB J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1007\/s00109-013-0993-5","article-title":"Ocular neovascularization","volume":"91","author":"Campochiaro","year":"2013","journal-title":"J. Mol. Med. (Berl)"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1480","DOI":"10.1056\/NEJM199412013312203","article-title":"Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders","volume":"331","author":"Aiello","year":"1994","journal-title":"N. Engl. J. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1016\/j.ophtha.2014.08.031","article-title":"Intravitreal aflibercept for macular edema following branch retinal vein occlusion: The 24-week results of the VIBRANT study","volume":"122","author":"Campochiaro","year":"2015","journal-title":"Ophthalmology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2044","DOI":"10.1016\/j.ophtha.2015.06.017","article-title":"Intravitreal Aflibercept for Diabetic Macular Edema: 100-Week Results From the VISTA and VIVID Studies","volume":"122","author":"Brown","year":"2015","journal-title":"Ophthalmology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1016\/S0140-6736(18)31550-2","article-title":"Age-related macular degeneration","volume":"392","author":"Mitchell","year":"2018","journal-title":"Lancet"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1432","DOI":"10.1056\/NEJMoa062655","article-title":"Ranibizumab versus verteporfin for neovascular age-related macular degeneration","volume":"355","author":"Brown","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.1056\/NEJMoa054481","article-title":"Ranibizumab for neovascular age-related macular degeneration","volume":"355","author":"Rosenfeld","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2537","DOI":"10.1016\/j.ophtha.2012.09.006","article-title":"Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration","volume":"119","author":"Heier","year":"2012","journal-title":"Ophthalmology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1097\/ICO.0b013e318201405a","article-title":"Treatments for corneal neovascularization: A review","volume":"30","author":"Gupta","year":"2011","journal-title":"Cornea"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1097\/00003226-199811000-00013","article-title":"In vivo confocal imaging of corneal neovascularization","volume":"17","author":"Yaylali","year":"1998","journal-title":"Cornea"},{"key":"ref_46","first-page":"2105","article-title":"The effect of total-body irradiation on corneal neovascularization in the Fischer 344 rat after chemical cauterization","volume":"32","author":"Scroggs","year":"1991","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1097\/IIO.0b013e31829ceefa","article-title":"Corneal alkali burns: A review of the literature and proposed protocol for evaluation and treatment","volume":"53","author":"Hamill","year":"2013","journal-title":"Int. Ophthalmol. Clin."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1080\/02713680902919557","article-title":"Mediators of neovascularization and the hypoxic cornea","volume":"34","author":"Safvati","year":"2009","journal-title":"Curr. Eye Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/j.jtos.2018.06.004","article-title":"Current and emerging therapies for corneal neovascularization","volume":"16","author":"Roshandel","year":"2018","journal-title":"Ocul. Surf."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.plipres.2011.06.001","article-title":"Glycerophospholipids and glycerophospholipid-derived lipid mediators: A complex meshwork in Alzheimer\u2019s disease pathology","volume":"50","author":"Frisardi","year":"2011","journal-title":"Prog. Lipid Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.plipres.2014.01.002","article-title":"Application of stable isotopes to investigate the metabolism of fatty acids, glycerophospholipid and sphingolipid species","volume":"54","author":"Ecker","year":"2014","journal-title":"Prog. Lipid Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.plipres.2011.02.004","article-title":"Mechanisms of glycerophospholipid homeostasis in mammalian cells","volume":"50","author":"Hermansson","year":"2011","journal-title":"Prog. Lipid Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1042\/bj3450061","article-title":"Characterization of plasma unsaturated lysophosphatidylcholines in human and rat","volume":"345 Pt 1","author":"Croset","year":"2000","journal-title":"Biochem. J."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.3390\/molecules15031354","article-title":"Synthesis of lysophospholipids","volume":"15","author":"Servi","year":"2010","journal-title":"Molecules"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1002\/bies.20081","article-title":"The ins and outs of lysophosphatidic acid signaling","volume":"26","author":"Moolenaar","year":"2004","journal-title":"Bioessays"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.molcel.2017.06.013","article-title":"Acylglycerol Kinase Mutated in Sengers Syndrome Is a Subunit of the TIM22 Protein Translocase in Mitochondria","volume":"67","author":"Vukotic","year":"2017","journal-title":"Mol. Cell"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.cellsig.2008.10.010","article-title":"Lysophosphatidic acid signaling in airway epithelium: Role in airway inflammation and remodeling","volume":"21","author":"Zhao","year":"2009","journal-title":"Cell. Signal."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1146\/annurev.pharmtox.010909.105753","article-title":"LPA receptors: Subtypes and biological actions","volume":"50","author":"Choi","year":"2010","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.lfs.2018.12.040","article-title":"The role of lysophosphatidic acid in the physiology and pathology of the skin","volume":"220","author":"Lei","year":"2019","journal-title":"Life Sci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"5073","DOI":"10.1242\/dev.126.22.5073","article-title":"Development of erythroid and myeloid progenitors in the yolk sac and embryo proper of the mouse","volume":"126","author":"Palis","year":"1999","journal-title":"Development"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/j.semcdb.2004.05.001","article-title":"Mechanisms of lysophosphatidic acid production","volume":"15","author":"Aoki","year":"2004","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1146\/annurev.pharmtox.41.1.507","article-title":"Lysophospholipid receptors","volume":"41","author":"Fukushima","year":"2001","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_63","first-page":"6938","article-title":"Autotaxin (NPP-2), a metastasis-enhancing motogen, is an angiogenic factor","volume":"61","author":"Nam","year":"2001","journal-title":"Cancer Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/S0090-6980(01)00105-8","article-title":"The LPA receptors","volume":"64","author":"Fukushima","year":"2001","journal-title":"Prostaglandins Other Lipid Mediat."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Lee, J.H., Kim, D., Oh, Y.S., and Jun, H.S. (2019). Lysophosphatidic Acid Signaling in Diabetic Nephropathy. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20112850"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1152\/physiolgenomics.00070.2017","article-title":"Role of lysophosphatidic acid and its receptors in the kidney","volume":"49","author":"Park","year":"2017","journal-title":"Physiol. Genomics"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Lin, K.H., Chiang, J.C., Ho, Y.H., Yao, C.L., and Lee, H. (2020). Lysophosphatidic Acid and Hematopoiesis: From Microenvironmental Effects to Intracellular Signaling. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21062015"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Yun, C.C. (2019). Lysophosphatidic Acid and Autotaxin-associated Effects on the Initiation and Progression of Colorectal Cancer. Cancers (Basel), 11.","DOI":"10.3390\/cancers11070958"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1194\/jlr.R046458","article-title":"LPA receptor signaling: Pharmacology, physiology, and pathophysiology","volume":"55","author":"Yung","year":"2014","journal-title":"J. Lipid Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1002\/iub.220","article-title":"Lysophosphatidic acid in vascular development and disease","volume":"61","author":"Teo","year":"2009","journal-title":"IUBMB Life"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"25822","DOI":"10.1074\/jbc.M605142200","article-title":"Autotaxin stabilizes blood vessels and is required for embryonic vasculature by producing lysophosphatidic acid","volume":"281","author":"Tanaka","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1126\/science.275.5299.533","article-title":"Vascular system defects and impaired cell chemokinesis as a result of Galpha13 deficiency","volume":"275","author":"Offermanns","year":"1997","journal-title":"Science"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"43972","DOI":"10.1074\/jbc.M111.301093","article-title":"Autotaxin regulates vascular development via multiple lysophosphatidic acid (LPA) receptors in zebrafish","volume":"286","author":"Yukiura","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1111\/j.1365-2443.2011.01546.x","article-title":"Impaired vascular remodeling in the yolk sac of embryos deficient in ROCK-I and ROCK-II","volume":"16","author":"Kamijo","year":"2011","journal-title":"Genes Cells"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Chuang, Y.W., Chang, W.M., Chen, K.H., Hong, C.Z., Chang, P.J., and Hsu, H.C. (2014). Lysophosphatidic acid enhanced the angiogenic capability of human chondrocytes by regulating Gi\/NF-kB-dependent angiogenic factor expression. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0095180"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/j.bbrc.2013.06.098","article-title":"Aromatic hydrocarbon receptor inhibits lysophosphatidic acid-induced vascular endothelial growth factor-A expression in PC-3 prostate cancer cells","volume":"437","author":"Wu","year":"2013","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1426","DOI":"10.1016\/j.bbalip.2013.05.003","article-title":"Lysophosphatidic acid promotes secretion of VEGF by increasing expression of 150-kD Oxygen-regulated protein (ORP150) in mesenchymal stem cells","volume":"1831","author":"Wei","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"6351","DOI":"10.1158\/1078-0432.CCR-06-1252","article-title":"Activation of hypoxia-inducible factor-1alpha is necessary for lysophosphatidic acid-induced vascular endothelial growth factor expression","volume":"12","author":"Lee","year":"2006","journal-title":"Clin. Cancer Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"7983","DOI":"10.1158\/0008-5472.CAN-05-4381","article-title":"Hypoxia enhances lysophosphatidic acid responsiveness in ovarian cancer cells and lysophosphatidic acid induces ovarian tumor metastasis in vivo","volume":"66","author":"Kim","year":"2006","journal-title":"Cancer Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.archoralbio.2007.08.006","article-title":"Lysophosphatidic acid-stimulated interleukin-6 and -8 synthesis through LPA1 receptors on human osteoblasts","volume":"53","author":"Aki","year":"2008","journal-title":"Arch. Oral. Biol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1002\/ijc.26476","article-title":"Lysophosphatidic acid receptor 2\/3-mediated IL-8-dependent angiogenesis in cervical cancer cells","volume":"131","author":"Chen","year":"2012","journal-title":"Int. J. Cancer"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"12536","DOI":"10.1074\/jbc.M109.099630","article-title":"Rho kinase-2 activation in human endothelial cells drives lysophosphatidic acid-mediated expression of cell adhesion molecules via NF-kappaB p65","volume":"285","author":"Shimada","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"R1174","DOI":"10.1152\/ajpregu.00619.2006","article-title":"Lysophosphatidic acid induces endothelial cell death by modulating the redox environment","volume":"292","author":"Brault","year":"2007","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1038\/nm1060","article-title":"Initiation of neuropathic pain requires lysophosphatidic acid receptor signaling","volume":"10","author":"Inoue","year":"2004","journal-title":"Nat. Med."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1260419","DOI":"10.1126\/science.1260419","article-title":"Proteomics. Tissue-based map of the human proteome","volume":"347","author":"Fagerberg","year":"2015","journal-title":"Science"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2468","DOI":"10.1093\/hmg\/ddq129","article-title":"Transcriptome analysis and molecular signature of human retinal pigment epithelium","volume":"19","author":"Strunnikova","year":"2010","journal-title":"Hum. Mol. Genet."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1002\/(SICI)1097-4695(199912)41:4<495::AID-NEU5>3.0.CO;2-K","article-title":"Lysophosphatidic acid-induced Ca(2+) mobilization in the neural retina of chick embryo","volume":"41","author":"Zhou","year":"1999","journal-title":"J. Neurobiol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1159\/000364858","article-title":"G-protein-coupled receptor cell signaling pathways mediating embryonic chick retinal growth cone collapse induced by lysophosphatidic acid and sphingosine-1-phosphate","volume":"36","author":"Fincher","year":"2014","journal-title":"Dev. Neurosci."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1016\/j.bbalip.2018.04.007","article-title":"Role of lysophosphatidic acid in the retinal pigment epithelium and photoreceptors","volume":"1863","author":"Lidgerwood","year":"2018","journal-title":"Biochim. Biophys. Acta. Mol. Cell Biol. Lipids"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"4332","DOI":"10.1172\/JCI121955","article-title":"Lysophosphatidic acid-induced YAP\/TAZ activation promotes developmental angiogenesis by repressing Notch ligand Dll4","volume":"129","author":"Yasuda","year":"2019","journal-title":"J. Clin. Investig."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1186\/1476-511X-13-187","article-title":"Expression of bioactive lysophospholipids and processing enzymes in the vitreous from patients with proliferative diabetic retinopathy","volume":"13","author":"Nawaz","year":"2014","journal-title":"Lipids Health Dis."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1007\/s00592-012-0422-1","article-title":"Expression of lysophosphatidic acid, autotaxin and acylglycerol kinase as biomarkers in diabetic retinopathy","volume":"50","author":"Mohammad","year":"2013","journal-title":"Acta Diabetol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"2311","DOI":"10.1097\/IAE.0000000000001112","article-title":"LYSOPHOSPHATIDIC ACIDS AND AUTOTAXIN IN RETINAL VEIN OCCLUSION","volume":"36","author":"Dacheva","year":"2016","journal-title":"Retina"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s12944-018-0954-7","article-title":"Serum lipids in adults with late age-related macular degeneration: A case-control study","volume":"18","author":"Semba","year":"2019","journal-title":"Lipids Health Dis."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1515\/hsz-2018-0237","article-title":"Sphingolipid metabolism - an ambiguous regulator of autophagy in the brain","volume":"399","author":"Alam","year":"2018","journal-title":"Biol. Chem."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Bandet, C.L., Tan-Chen, S., Bourron, O., Le Stunff, H., and Hajduch, E. (2019). Sphingolipid Metabolism: New Insight into Ceramide-Induced Lipotoxicity in Muscle Cells. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20030479"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1038\/nrm2329","article-title":"Principles of bioactive lipid signalling: Lessons from sphingolipids","volume":"9","author":"Hannun","year":"2008","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.jbior.2016.10.002","article-title":"Ceramidases, roles in sphingolipid metabolism and in health and disease","volume":"63","author":"Coant","year":"2017","journal-title":"Adv. Biol. Regul."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1002\/jcb.20127","article-title":"Structural and functional characteristics of S1P receptors","volume":"92","author":"Sanchez","year":"2004","journal-title":"J. Cell Biochem."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1124\/pr.107.07113","article-title":"\u201cInside-out\u201d signaling of sphingosine-1-phosphate: Therapeutic targets","volume":"60","author":"Takabe","year":"2008","journal-title":"Pharmacol. Rev."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1038\/nrm1103","article-title":"Sphingosine-1-phosphate: An enigmatic signalling lipid","volume":"4","author":"Spiegel","year":"2003","journal-title":"Nat. Rev. Mol. Cell. Biol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.advenzreg.2010.09.004","article-title":"Sphingosine kinase localization in the control of sphingolipid metabolism","volume":"51","author":"Siow","year":"2011","journal-title":"Adv. Enzyme Regul."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1096\/fj.10-167502","article-title":"Sphingosine-1-phosphate produced by sphingosine kinase 2 in mitochondria interacts with prohibitin 2 to regulate complex IV assembly and respiration","volume":"25","author":"Strub","year":"2011","journal-title":"FASEB J."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"e12836","DOI":"10.1111\/cmi.12836","article-title":"Sphingosine-1-phosphate receptors and innate immunity","volume":"20","author":"Bryan","year":"2018","journal-title":"Cell Microbiol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1006\/geno.1998.5491","article-title":"EDG6, a novel G-protein-coupled receptor related to receptors for bioactive lysophospholipids, is specifically expressed in lymphoid tissue","volume":"53","author":"Bernhardt","year":"1998","journal-title":"Genomics"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"14281","DOI":"10.1074\/jbc.275.19.14281","article-title":"Characterization of a novel sphingosine 1-phosphate receptor, Edg-8","volume":"275","author":"Im","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1186\/s12967-020-02322-y","article-title":"Serum sphingosine-1-phosphate levels and Sphingosine-1-Phosphate gene polymorphisms in acute respiratory distress syndrome: A multicenter prospective study","volume":"18","author":"Zhao","year":"2020","journal-title":"J. Transl. Med."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"3071","DOI":"10.1111\/trf.15494","article-title":"Analyses of sphingosine-1-phosphate in the context of transfusion: How much is in stored blood products and in patient blood?","volume":"59","author":"Poppe","year":"2019","journal-title":"Transfusion"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1096\/fj.06-7433com","article-title":"Erythrocytes store and release sphingosine 1-phosphate in blood","volume":"21","year":"2007","journal-title":"FASEB J."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"11113","DOI":"10.1128\/MCB.25.24.11113-11121.2005","article-title":"Essential role for sphingosine kinases in neural and vascular development","volume":"25","author":"Mizugishi","year":"2005","journal-title":"Mol. Cell Biol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1172\/JCI10905","article-title":"Edg-1, the G protein-coupled receptor for sphingosine-1-phosphate, is essential for vascular maturation","volume":"106","author":"Liu","year":"2000","journal-title":"J. Clin. Investig."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"29367","DOI":"10.1074\/jbc.M403937200","article-title":"The sphingosine-1-phosphate receptors S1P1, S1P2, and S1P3 function coordinately during embryonic angiogenesis","volume":"279","author":"Kono","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1503206","DOI":"10.1155\/2016\/1503206","article-title":"Sphingosine-1-Phosphate\/Sphingosine-1-Phosphate Receptor 2 Axis Can Promote Mouse and Human Primary Mast Cell Angiogenic Potential through Upregulation of Vascular Endothelial Growth Factor-A and Matrix Metalloproteinase-2","volume":"2016","author":"Chumanevich","year":"2016","journal-title":"Mediat. Inflamm."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1757","DOI":"10.1007\/s00417-017-3711-0","article-title":"Hypoxia and inflammation in the release of VEGF and interleukins from human retinal pigment epithelial cells","volume":"255","author":"Arjamaa","year":"2017","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Kalhori, V., Kemppainen, K., Asghar, M.Y., Bergelin, N., Jaakkola, P., and T\u00f6rnquist, K. (2013). Sphingosine-1-Phosphate as a Regulator of Hypoxia-Induced Factor-1\u03b1 in Thyroid Follicular Carcinoma Cells. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0066189"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"F271","DOI":"10.1152\/ajprenal.00071.2006","article-title":"Hypoxia-inducible factors in the kidney","volume":"291","author":"Haase","year":"2006","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"3365","DOI":"10.1074\/jbc.M708241200","article-title":"Sphingosine kinase 1 is up-regulated during hypoxia in U87MG glioma cells. Role of hypoxia-inducible factors 1 and 2","volume":"283","author":"Anelli","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"8200","DOI":"10.1167\/iovs.12-10965","article-title":"Sphingosine 1-phosphate elicits proinflammatory responses in ARPE-19 cells","volume":"53","author":"Qiao","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"O\u2019Sullivan, M.J., Hirota, N., and Martin, J.G. (2014). Sphingosine 1-phosphate (S1P) induced interleukin-8 (IL-8) release is mediated by S1P receptor 2 and nuclear factor \u03baB in BEAS-2B cells. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0095566"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/S0092-8674(00)81661-X","article-title":"Vascular endothelial cell adherens junction assembly and morphogenesis induced by sphingosine-1-phosphate","volume":"99","author":"Lee","year":"1999","journal-title":"Cell"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.1161\/ATVBAHA.107.143735","article-title":"Induction of vascular permeability by the sphingosine-1-phosphate receptor-2 (S1P2R) and its downstream effectors ROCK and PTEN","volume":"27","author":"Sanchez","year":"2007","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"4312","DOI":"10.1073\/pnas.0409784102","article-title":"PTEN as an effector in the signaling of antimigratory G protein-coupled receptor","volume":"102","author":"Sanchez","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Terao, R., Honjo, M., Ueta, T., Obinata, H., Izumi, T., Kurano, M., Yatomi, Y., Koso, H., Watanabe, S., and Aihara, M. (2019). Light Stress-Induced Increase of Sphingosine 1-Phosphate in Photoreceptors and Its Relevance to Retinal Degeneration. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20153670"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/j.devcel.2012.08.005","article-title":"The sphingosine-1-phosphate receptor S1PR1 restricts sprouting angiogenesis by regulating the interplay between VE-cadherin and VEGFR2","volume":"23","author":"Gaengel","year":"2012","journal-title":"Dev. Cell"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1016\/j.devcel.2020.01.016","article-title":"Sphingosine 1-Phosphate Receptor Signaling Establishes AP-1 Gradients to Allow for Retinal Endothelial Cell Specialization","volume":"52","author":"Yanagida","year":"2020","journal-title":"Dev. Cell"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1167\/iovs.17-22544","article-title":"Sphingosine Kinase 2 Modulates Retinal Neovascularization in the Mouse Model of Oxygen-Induced Retinopathy","volume":"59","author":"Eresch","year":"2018","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"2506","DOI":"10.1172\/JCI31123","article-title":"Essential role of sphingosine 1-phosphate receptor 2 in pathological angiogenesis of the mouse retina","volume":"117","author":"Skoura","year":"2007","journal-title":"J. Clin. Investig."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1002\/jcp.21588","article-title":"Blockade of sphingosine-1-phosphate reduces macrophage influx and retinal and choroidal neovascularization","volume":"218","author":"Xie","year":"2009","journal-title":"J. Cell Physiol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"2245","DOI":"10.1194\/jlr.M900048-JLR200","article-title":"Production and characterization of monoclonal anti-sphingosine-1-phosphate antibodies","volume":"50","author":"Jones","year":"2009","journal-title":"J. Lipid Res."},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Terao, R., Honjo, M., and Aihara, M. (2017). Apolipoprotein M Inhibits Angiogenic and Inflammatory Response by Sphingosine 1-Phosphate on Retinal Pigment Epithelium Cells. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19010112"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"106365","DOI":"10.1016\/j.prostaglandins.2019.106365","article-title":"The role of sphingosine 1-phosphate receptors on retinal pigment epithelial cells barrier function and angiogenic effects","volume":"145","author":"Terao","year":"2019","journal-title":"Prostaglandins Other Lipid Mediat."},{"key":"ref_132","unstructured":"(2011). Efficacy and Safety Study of iSONEP with & without Lucentis\/Avastin\/Eylea to Treat Wet AMD, Lpath, Inc.. Available online: https:\/\/ClinicalTrials.gov\/show\/NCT01414153."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1016\/j.bcp.2008.12.007","article-title":"Involvement of sphingosine-1-phosphate and S1P1 in angiogenesis: Analyses using a new S1P1 antagonist of non-sphingosine-1-phosphate analog","volume":"77","author":"Yonesu","year":"2009","journal-title":"Biochem. Pharmacol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1158\/0008-5472.CAN-05-2001","article-title":"Antagonism of sphingosine-1-phosphate receptors by FTY720 inhibits angiogenesis and tumor vascularization","volume":"66","author":"LaMontagne","year":"2006","journal-title":"Cancer Res."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.dci.2017.12.005","article-title":"Eicosanoid-mediated immunity in insects","volume":"83","author":"Kim","year":"2018","journal-title":"Dev. Comp. Immunol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.plefa.2018.03.004","article-title":"Omega-6 fatty acids and inflammation","volume":"132","author":"Innes","year":"2018","journal-title":"Prostaglandins Leukot. Essent. Fatty Acids"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.prostaglandins.2016.12.004","article-title":"Chemistry and biology of \u03c9-3 PUFA peroxidation-derived compounds","volume":"132","author":"Wang","year":"2017","journal-title":"Prostaglandins Other Lipid Mediat."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.plefa.2005.02.004","article-title":"New insights into the retinal circulation: Inflammatory lipid mediators in ischemic retinopathy","volume":"72","author":"Hardy","year":"2005","journal-title":"Prostaglandins Leukot. Essent. Fatty Acids"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/j.brainresbull.2009.10.018","article-title":"The effects of nepafenac and amfenac on retinal angiogenesis","volume":"81","author":"Yanni","year":"2010","journal-title":"Brain Res. Bull."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1096\/fj.201600604r","article-title":"In vivo studies validating multitargeting of prostanoid receptors for achieving superior anti-inflammatory effects","volume":"31","author":"Woodward","year":"2017","journal-title":"FASEB J."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1007\/s00404-020-05559-6","article-title":"COX-2-PGE(2)-EPs in gynecological cancers","volume":"301","author":"Ye","year":"2020","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"C652","DOI":"10.1152\/ajpcell.1989.256.3.C652","article-title":"Regulation of cAMP metabolism by PGE2 in cortical and medullary thick ascending limb of Henle\u2019s loop","volume":"256","author":"Nakao","year":"1989","journal-title":"Am. J. Physiol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1038\/365166a0","article-title":"Alternative splicing of C-terminal tail of prostaglandin E receptor subtype EP3 determines G-protein specificity","volume":"365","author":"Namba","year":"1993","journal-title":"Nature"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1016\/j.biocel.2003.08.006","article-title":"Prostanoids and prostanoid receptors in signal transduction","volume":"36","author":"Bos","year":"2004","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1248\/yakushi.123.295","article-title":"Regulation by prostaglandin E2 and histamine of angiogenesis in inflammatory granulation tissue","volume":"123","author":"Ghosh","year":"2003","journal-title":"Yakugaku Zasshi"},{"key":"ref_146","doi-asserted-by":"crossref","unstructured":"Majumder, M., Nandi, P., Omar, A., Ugwuagbo, K.C., and Lala, P.K. (2018). EP4 as a Therapeutic Target for Aggressive Human Breast Cancer. Int. J. Mol. Sci., 19.","DOI":"10.20944\/preprints201802.0095.v1"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"e969154","DOI":"10.4161\/23723548.2014.969154","article-title":"Improving VEGF-targeted therapies through inhibition of COX-2\/PGE2 signaling","volume":"1","author":"Xu","year":"2014","journal-title":"Mol. Cell Oncol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/j.bbrc.2014.08.032","article-title":"PGE2-induced colon cancer growth is mediated by mTORC1","volume":"451","author":"Dufour","year":"2014","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"14656","DOI":"10.1038\/ncomms14656","article-title":"Activation of E-prostanoid 3 receptor in macrophages facilitates cardiac healing after myocardial infarction","volume":"8","author":"Tang","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1016\/j.bbrc.2008.10.140","article-title":"Human EP3(I) prostanoid receptor induces VEGF and VEGF receptor-1 mRNA expression","volume":"377","author":"Taniguchi","year":"2008","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1089\/jop.2018.0077","article-title":"In Vivo Choroidal Neovascularization and Macrophage Studies Provide Further Evidence for a Broad Role of Prostacyclin in Angiogenesis","volume":"35","author":"Woodward","year":"2019","journal-title":"J. Ocul. Pharmacol. Ther."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"2002","DOI":"10.2174\/1381612824666180629111227","article-title":"Roles of Cyclooxygenase, Prostaglandin E2 and EP Receptors in Mucosal Protection and Ulcer Healing in the Gastrointestinal Tract","volume":"24","author":"Takeuchi","year":"2018","journal-title":"Curr. Pharm. Des."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1071\/RD12112","article-title":"Targeting angiogenesis in the pathological ovary","volume":"25","author":"Duncan","year":"2013","journal-title":"Reprod. Fertil. Dev."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"2388","DOI":"10.4049\/jimmunol.141.7.2388","article-title":"Release of tumor necrosis factor-alpha from macrophages. Enhancement and suppression are dose-dependently regulated by prostaglandin E2 and cyclic nucleotides","volume":"141","author":"Renz","year":"1988","journal-title":"J. Immunol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"7463","DOI":"10.1158\/0008-5472.CAN-11-2449","article-title":"PGE(2)-induced CXCL12 production and CXCR4 expression controls the accumulation of human MDSCs in ovarian cancer environment","volume":"71","author":"Obermajer","year":"2011","journal-title":"Cancer Res."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.exer.2010.03.019","article-title":"Genetic deletion of COX-2 diminishes VEGF production in mouse retinal M\u00fcller cells","volume":"91","author":"Yanni","year":"2010","journal-title":"Exp. Eye Res."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1161\/ATVBAHA.116.308587","article-title":"E-Prostanoid 3 Receptor Mediates Sprouting Angiogenesis Through Suppression of the Protein Kinase A\/\u03b2-Catenin\/Notch Pathway","volume":"37","author":"Chen","year":"2017","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"5479","DOI":"10.1167\/iovs.09-3652","article-title":"The role of PGE2 receptor EP4 in pathologic ocular angiogenesis","volume":"50","author":"Yanni","year":"2009","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"6311","DOI":"10.1167\/iovs.10-5455","article-title":"Selective activation of the prostaglandin E2 circuit in chronic injury-induced pathologic angiogenesis","volume":"51","author":"Liclican","year":"2010","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1167\/iovs.02-0392","article-title":"COX-2 inhibition and retinal angiogenesis in a mouse model of retinopathy of prematurity","volume":"44","author":"Alousis","year":"2003","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/j.bbrc.2004.10.054","article-title":"COX-2-selective inhibitor, etodolac, suppresses choroidal neovascularization in a mice model","volume":"325","author":"Takahashi","year":"2004","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1076\/ceyr.19.4.300.5301","article-title":"The effect of selective cyclooxygenase-2 inhibitor on corneal angiogenesis in the rat","volume":"19","author":"Yamada","year":"1999","journal-title":"Curr. Eye Res."},{"key":"ref_163","doi-asserted-by":"crossref","unstructured":"Serini, S., Ottes Vasconcelos, R., Nascimento Gomes, R., and Calviello, G. (2017). Protective Effects of \u03c9-3 PUFA in Anthracycline-Induced Cardiotoxicity: A Critical Review. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18122689"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.preteyeres.2004.06.002","article-title":"The role of omega-3 long-chain polyunsaturated fatty acids in health and disease of the retina","volume":"24","author":"SanGiovanni","year":"2005","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"4342","DOI":"10.1167\/iovs.05-0601","article-title":"Anti-inflammatory effect of docosahexaenoic acid on cytokine-induced adhesion molecule expression in human retinal vascular endothelial cells","volume":"46","author":"Chen","year":"2005","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1161\/CIRCRESAHA.110.221317","article-title":"Short communication: PPAR gamma mediates a direct antiangiogenic effect of omega 3-PUFAs in proliferative retinopathy","volume":"107","author":"Stahl","year":"2010","journal-title":"Circ. Res."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/10408398.2011.565523","article-title":"Bioactive lipids in pathological retinopathy","volume":"54","author":"Ma","year":"2014","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"724","DOI":"10.2337\/db19-0550","article-title":"n-3 Fatty Acid and Its Metabolite 18-HEPE Ameliorate Retinal Neuronal Cell Dysfunction by Enhancing M\u00fcller BDNF in Diabetic Retinopathy","volume":"69","author":"Suzumura","year":"2020","journal-title":"Diabetes"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1038\/nm1591","article-title":"Increased dietary intake of omega-3-polyunsaturated fatty acids reduces pathological retinal angiogenesis","volume":"13","author":"Connor","year":"2007","journal-title":"Nat. Med."},{"key":"ref_170","first-page":"2309","article-title":"Peroxisome proliferator-activated receptor-gamma ligands inhibit choroidal neovascularization","volume":"41","author":"Murata","year":"2000","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_171","doi-asserted-by":"crossref","unstructured":"SanGiovanni, J.P., Chen, J., Sapieha, P., Aderman, C.M., Stahl, A., Clemons, T.E., Chew, E.Y., and Smith, L.E. (2013). DNA sequence variants in PPARGC1A, a gene encoding a coactivator of the \u03c9-3 LCPUFA sensing PPAR-RXR transcription complex, are associated with NV AMD and AMD-associated loci in genes of complement and VEGF signaling pathways. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0053155"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"1601","DOI":"10.3945\/ajcn.2009.27594","article-title":"{omega}-3 Long-chain polyunsaturated fatty acid intake and 12-y incidence of neovascular age-related macular degeneration and central geographic atrophy: AREDS report 30, a prospective cohort study from the Age-Related Eye Disease Study","volume":"90","author":"Sangiovanni","year":"2009","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1093\/ajcn\/88.2.398","article-title":"Oily fish consumption, dietary docosahexaenoic acid and eicosapentaenoic acid intakes, and associations with neovascular age-related macular degeneration","volume":"88","author":"Augood","year":"2008","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"e0132643","DOI":"10.1371\/journal.pone.0132643","article-title":"Optimization of an Image-Guided Laser-Induced Choroidal Neovascularization Model in Mice","volume":"10","author":"Gong","year":"2015","journal-title":"PLoS ONE"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1016\/j.ajo.2014.07.036","article-title":"Omega-3 supplementation combined with anti-vascular endothelial growth factor lowers vitreal levels of vascular endothelial growth factor in wet age-related macular degeneration","volume":"158","author":"Rezende","year":"2014","journal-title":"Am. J. Ophthalmol."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.4049\/jimmunol.1003456","article-title":"Controlling herpes simplex virus-induced ocular inflammatory lesions with the lipid-derived mediator resolvin E1","volume":"186","author":"Rajasagi","year":"2011","journal-title":"J. Immunol."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"4743","DOI":"10.1167\/iovs.08-2462","article-title":"Anti-angiogenesis effect of the novel anti-inflammatory and pro-resolving lipid mediators","volume":"50","author":"Jin","year":"2009","journal-title":"Investig. Ophthalmol. Vis. Sci."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/13\/4758\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:47:18Z","timestamp":1760176038000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/13\/4758"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,4]]},"references-count":177,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2020,7]]}},"alternative-id":["ijms21134758"],"URL":"https:\/\/doi.org\/10.3390\/ijms21134758","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,4]]}}}