{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T06:19:22Z","timestamp":1768717162541,"version":"3.49.0"},"reference-count":35,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,20]],"date-time":"2023-02-20T00:00:00Z","timestamp":1676851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81470654"],"award-info":[{"award-number":["81470654"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2019SF-047"],"award-info":[{"award-number":["2019SF-047"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007128","name":"Natural Science Foundation of Shaanxi Province","doi-asserted-by":"publisher","award":["81470654"],"award-info":[{"award-number":["81470654"]}],"id":[{"id":"10.13039\/501100007128","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007128","name":"Natural Science Foundation of Shaanxi Province","doi-asserted-by":"publisher","award":["2019SF-047"],"award-info":[{"award-number":["2019SF-047"]}],"id":[{"id":"10.13039\/501100007128","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Age-related macular degeneration (AMD) is the most common blindness-causing disease among the elderly. Under oxidative stress, low-density lipoprotein in the outer layer of the retina is easily converted into oxidized low-density lipoprotein (OxLDL), which promotes the development of choroidal neovascularization (CNV), the main pathological change in wet AMD. Liver X receptor (LXR), a ligand-activated nuclear transcription factor, regulates various processes related to CNV, including lipid metabolism, cholesterol transport, inflammation, and angiogenesis. In this study, we evaluated the effects of the LXR agonist TO901317 (TO) on CNV. Our results demonstrated that the TO could inhibit OxLDL-induced CNV in mice as well as inflammation and angiogenesis in vitro. Using siRNA transfection in cells and Vldlr\u2212\/\u2212 mice, we further confirmed the inhibitory effects of TO against the inflammatory response and oxidative stress. Mechanistically, the LXR agonist reduces the inflammatory response via the nuclear translocation of NF-\u03baB p65 in the pathway for NF-\u03baB activation and by enhancing ABCG1-dependent lipid transportation. Therefore, an LXR agonist is a promising therapeutic candidate for AMD, especially for wet AMD.<\/jats:p>","DOI":"10.3390\/jcm12041674","type":"journal-article","created":{"date-parts":[[2023,2,20]],"date-time":"2023-02-20T02:56:02Z","timestamp":1676861762000},"page":"1674","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Liver X Receptor Agonist Inhibits Oxidized Low-Density Lipoprotein Induced Choroidal Neovascularization via the NF-\u03baB Signaling Pathway"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9742-4648","authenticated-orcid":false,"given":"Tong","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Eye Institute of Chinese PLA, Xijing Hospital, Fourth Military Medical University, Xi\u2019an 710032, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinli","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Eye Institute of Chinese PLA, Xijing Hospital, Fourth Military Medical University, Xi\u2019an 710032, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kuanrong","family":"Dang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Eye Institute of Chinese PLA, Xijing Hospital, Fourth Military Medical University, Xi\u2019an 710032, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengzhang","family":"Tao","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Eye Institute of Chinese PLA, Xijing Hospital, Fourth Military Medical University, Xi\u2019an 710032, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baozhen","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Histology and Embryology, Xi\u2019an Health School, Xi\u2019an 710032, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao","family":"Chen","sequence":"additional","affiliation":[{"name":"Center of Clinical Aerospace Medicine, Fourth Military Medical University, Xi\u2019an 710032, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zuoming","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center of Clinical Aerospace Medicine, Fourth Military Medical University, Xi\u2019an 710032, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Eye Institute of Chinese PLA, Xijing Hospital, Fourth Military Medical University, Xi\u2019an 710032, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongjun","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Eye Institute of Chinese PLA, Xijing Hospital, Fourth Military Medical University, Xi\u2019an 710032, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e106","DOI":"10.1016\/S2214-109X(13)70145-1","article-title":"Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: A systematic review and meta-analysis","volume":"2","author":"Wong","year":"2014","journal-title":"Lancet Glob. Health"},{"key":"ref_2","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_3","doi-asserted-by":"crossref","first-page":"100858","DOI":"10.1016\/j.preteyeres.2020.100858","article-title":"Mechanisms of mitochondrial dysfunction and their impact on age-related macular degeneration","volume":"79","author":"Kaarniranta","year":"2020","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1038\/nm1709","article-title":"Oxidative damage-induced inflammation initiates age-related macular degeneration","volume":"14","author":"Hollyfield","year":"2008","journal-title":"Nat. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4222","DOI":"10.1074\/jbc.M509769200","article-title":"Light-induced oxidation of photoreceptor outer segment phospholipids generates ligands for CD36-mediated phagocytosis by retinal pigment epithelium: A potential mechanism for modulating outer segment phagocytosis under oxidant stress conditions","volume":"281","author":"Sun","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Gu, X., Neric, N.J., Crabb, J.S., Crabb, J.W., Bhattacharya, S.K., Rayborn, M.E., Hollyfield, J.G., and Bonilha, V.L. (2012). Age-related changes in the retinal pigment epithelium (RPE). PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0038673"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2203","DOI":"10.1016\/j.ophtha.2011.04.029","article-title":"Risk models for progression to advanced age-related macular degeneration using demographic, environmental, genetic, and ocular factors","volume":"118","author":"Seddon","year":"2011","journal-title":"Ophthalmology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1016\/j.bbalip.2016.07.013","article-title":"Lipids, oxidized lipids, oxidation-specific epitopes, and Age-related Macular Degeneration","volume":"1862","author":"Handa","year":"2017","journal-title":"Biochim. Biophys. Acta. Mol. Cell Biol. Lipids"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.exer.2016.09.009","article-title":"Serum Paraoxonase activity in relation to lipid profile in Age-related Macular Degeneration patients","volume":"152","author":"AnandBabu","year":"2016","journal-title":"Exp. Eye Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/s10238-004-0054-z","article-title":"Changes in lipid metabolism in women with age-related macular degeneration","volume":"4","author":"Nowak","year":"2005","journal-title":"Clin. Exp. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1038\/s41586-018-0198-8","article-title":"Oxidized phospholipids are proinflammatory and proatherogenic in hypercholesterolaemic mice","volume":"558","author":"Que","year":"2018","journal-title":"Nature"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1161\/ATVBAHA.114.303887","article-title":"Oxidized low-density lipoprotein induces long-term proinflammatory cytokine production and foam cell formation via epigenetic reprogramming of monocytes","volume":"34","author":"Bekkering","year":"2014","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.18240\/ijo.2020.08.03","article-title":"A modified laser-induced choroidal neovascularization animal model with intravitreal oxidized low-density lipoprotein","volume":"13","author":"Wu","year":"2020","journal-title":"Int. J. Ophthalmol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1126\/science.1168974","article-title":"LXR regulates cholesterol uptake through Idol-dependent ubiquitination of the LDL receptor","volume":"325","author":"Zelcer","year":"2009","journal-title":"Science"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1688","DOI":"10.1172\/JCI59817","article-title":"Liver LXR\u03b1 expression is crucial for whole body cholesterol homeostasis and reverse cholesterol transport in mice","volume":"122","author":"Zhang","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1161\/01.RES.0000170946.56981.5c","article-title":"New insights into the regulation of HDL metabolism and reverse cholesterol transport","volume":"96","author":"Lewis","year":"2005","journal-title":"Circ. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1161\/CIRCRESAHA.119.316424","article-title":"LDL Receptor Regulates the Reverse Transport of Macrophage-Derived Unesterified Cholesterol via Concerted Action of the HDL-LDL Axis: Insight From Mouse Models","volume":"127","author":"Metso","year":"2020","journal-title":"Circ. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"7604","DOI":"10.1073\/pnas.112059299","article-title":"Synthetic LXR ligand inhibits the development of atherosclerosis in mice","volume":"99","author":"Joseph","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"11896","DOI":"10.1073\/pnas.182199799","article-title":"Identification of macrophage liver X receptors as inhibitors of atherosclerosis","volume":"99","author":"Tangirala","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"990","DOI":"10.18240\/ijo.2021.07.05","article-title":"Retinal neovascularization induced by mutant Vldlr gene inhibited in an inherited retinitis pigmentosa mouse model: An in-vivo study","volume":"14","author":"Yan","year":"2021","journal-title":"Int. J. Ophthalmol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"6525","DOI":"10.1167\/iovs.14-15067","article-title":"Reliability of the mouse model of choroidal neovascularization induced by laser photocoagulation","volume":"55","author":"Poor","year":"2014","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.3389\/fimmu.2019.01412","article-title":"Structural Basis of IL-1 Family Cytokine Signaling","volume":"10","author":"Fields","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"107931","DOI":"10.1016\/j.exer.2020.107931","article-title":"Gypenosides mediate cholesterol efflux and suppress oxidized LDL induced inflammation in retinal pigment epithelium cells","volume":"191","author":"Biswas","year":"2020","journal-title":"Exp. Eye Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5520644","DOI":"10.1155\/2021\/5520644","article-title":"P2X7 Receptor Antagonist Attenuates Retinal Inflammation and Neovascularization Induced by Oxidized Low-Density Lipoprotein","volume":"2021","author":"Yang","year":"2021","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1002\/path.4266","article-title":"Mechanisms of age-related macular degeneration and therapeutic opportunities","volume":"232","author":"LeCouter","year":"2014","journal-title":"J. Pathol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2989","DOI":"10.7150\/ijbs.49890","article-title":"The Role of Inflammation in Age-Related Macular Degeneration","volume":"16","author":"Tan","year":"2020","journal-title":"Int. J. Biol. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1016\/j.ophtha.2007.07.031","article-title":"Cardiovascular disease and hypertension are strong risk factors for choroidal neovascularization","volume":"115","author":"Hogg","year":"2008","journal-title":"Ophthalmology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"13757","DOI":"10.1073\/pnas.1121309109","article-title":"Complement factor H genotypes impact risk of age-related macular degeneration by interaction with oxidized phospholipids","volume":"109","author":"Shaw","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1161\/ATVBAHA.109.191197","article-title":"Liver x receptor signaling pathways and atherosclerosis","volume":"30","author":"Calkin","year":"2010","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e131928","DOI":"10.1172\/jci.insight.131928","article-title":"LXRs regulate features of age-related macular degeneration and may be a potential therapeutic target","volume":"5","author":"Choudhary","year":"2020","journal-title":"JCI Insight"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4617","DOI":"10.1007\/s00018-014-1709-x","article-title":"Emerging roles for nuclear receptors in the pathogenesis of age-related macular degeneration","volume":"71","author":"Malek","year":"2014","journal-title":"Cell. Mol. Life Sci. CMLS"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1038\/ng.3448","article-title":"A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants","volume":"48","author":"Fritsche","year":"2016","journal-title":"Nat. Genet."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1167\/iovs.61.12.24","article-title":"Fursultiamine Alleviates Choroidal Neovascularization by Suppressing Inflammation and Metabolic Reprogramming","volume":"61","author":"Do","year":"2020","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"a001651","DOI":"10.1101\/cshperspect.a001651","article-title":"The nuclear factor NF-kappaB pathway in inflammation","volume":"1","author":"Lawrence","year":"2009","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.cell.2008.01.020","article-title":"Shared principles in NF-kappaB signaling","volume":"132","author":"Hayden","year":"2008","journal-title":"Cell"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/4\/1674\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:36:57Z","timestamp":1760121417000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/4\/1674"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,20]]},"references-count":35,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["jcm12041674"],"URL":"https:\/\/doi.org\/10.3390\/jcm12041674","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,20]]}}}