{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T10:36:11Z","timestamp":1762079771022,"version":"build-2065373602"},"reference-count":65,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2022,12,9]],"date-time":"2022-12-09T00:00:00Z","timestamp":1670544000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Retina Research Foundation","award":["R01EY025641","R01EY031939"],"award-info":[{"award-number":["R01EY025641","R01EY031939"]}]},{"DOI":"10.13039\/100000053","name":"NIH\/NEI","doi-asserted-by":"publisher","award":["R01EY025641","R01EY031939"],"award-info":[{"award-number":["R01EY025641","R01EY031939"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Carl Marshall Reeves &amp; Mildred Almen Reeves Foundation","award":["R01EY025641","R01EY031939"],"award-info":[{"award-number":["R01EY025641","R01EY031939"]}]},{"name":"Indiana Center for Biomedical Innovation","award":["R01EY025641","R01EY031939"],"award-info":[{"award-number":["R01EY025641","R01EY031939"]}]},{"name":"Research to Prevent Blindness","award":["R01EY025641","R01EY031939"],"award-info":[{"award-number":["R01EY025641","R01EY031939"]}]},{"name":"Eli Lilly-Stark Neurosciences Predoctoral Research Fellowship in Neurodegeneration","award":["R01EY025641","R01EY031939"],"award-info":[{"award-number":["R01EY025641","R01EY031939"]}]},{"name":"PhRMA Foundation Predoctoral Fellowship in Pharmacology\/Toxicology","award":["R01EY025641","R01EY031939"],"award-info":[{"award-number":["R01EY025641","R01EY031939"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Neovascular or \u201cwet\u201d age-related macular degeneration (nAMD) is a leading cause of blindness among older adults. Choroidal neovascularization (CNV) is a major pathological feature of nAMD, in which abnormal new blood vessel growth from the choroid leads to irreversible vision loss. There is a critical need to develop novel therapeutic strategies to address limitations of the current anti-vascular endothelial growth factor biologics. Previously, we identified soluble epoxide hydrolase (sEH) as a possible therapeutic target for CNV through a forward chemical genetic approach. The purpose of this study was to validate sEH as a target by examining retinal expression of sEH protein and mRNA by immunohistochemistry and RNAscope in situ hybridization, respectively, and to assess the efficacy of an adeno-associated virus (AAV) vector designed to knock down the sEH gene, Ephx2, in the murine laser-induced (L-) CNV model. nAMD patient postmortem eye tissue and murine L-CNV showed overexpression of sEH in photoreceptors and retinal pigment epithelial cells. Ephx2 knockdown significantly reduced CNV and normalized mRNA expression levels of CNV-related inflammatory markers. Thus, this study further establishes sEH as a promising therapeutic target against CNV associated with nAMD.<\/jats:p>","DOI":"10.3390\/ijms232415595","type":"journal-article","created":{"date-parts":[[2022,12,9]],"date-time":"2022-12-09T02:50:51Z","timestamp":1670554251000},"page":"15595","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Decreased Expression of Soluble Epoxide Hydrolase Suppresses Murine Choroidal Neovascularization"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1440-7066","authenticated-orcid":false,"given":"Bomina","family":"Park","sequence":"first","affiliation":[{"name":"Eugene and Marilyn Glick Eye Institute, Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, IN 46202, USA"},{"name":"Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheik Pran Babu","family":"Sardar Pasha","sequence":"additional","affiliation":[{"name":"Eugene and Marilyn Glick Eye Institute, Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1525-0155","authenticated-orcid":false,"given":"Kamakshi L.","family":"Sishtla","sequence":"additional","affiliation":[{"name":"Eugene and Marilyn Glick Eye Institute, Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2061-411X","authenticated-orcid":false,"given":"Gabriella D.","family":"Hartman","sequence":"additional","affiliation":[{"name":"Eugene and Marilyn Glick Eye Institute, Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, IN 46202, USA"},{"name":"Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoping","family":"Qi","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0796-1766","authenticated-orcid":false,"given":"Michael E.","family":"Boulton","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1402-7875","authenticated-orcid":false,"given":"Timothy W.","family":"Corson","sequence":"additional","affiliation":[{"name":"Eugene and Marilyn Glick Eye Institute, Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, IN 46202, USA"},{"name":"Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN 46202, USA"},{"name":"Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA"},{"name":"Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1056\/NEJMcp2102061","article-title":"Age-related macular degeneration","volume":"385","author":"Apte","year":"2021","journal-title":"New. Engl. J. Med."},{"key":"ref_2","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_3","first-page":"533","article-title":"Vision Health Cost-Effectiveness Study Group, Forecasting age-related macular degeneration through the year 2050: The potential impact of new treatments","volume":"127","author":"Rein","year":"2009","journal-title":"JAMA Ophthalmol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3033","DOI":"10.1172\/JCI42437","article-title":"Therapeutic targets in age-related macular disease","volume":"120","author":"Bird","year":"2010","journal-title":"J. Clin. Investig."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"473","DOI":"10.2147\/CIA.S2777","article-title":"Age-related macular degeneration and the aging eye","volume":"3","author":"Ehrlich","year":"2008","journal-title":"Clin. Interv. Aging"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"546826","DOI":"10.1155\/2010\/546826","article-title":"Inflammatory mediators and angiogenic factors in choroidal neovascularization: Pathogenetic interactions and therapeutic implications","volume":"2010","author":"Campa","year":"2010","journal-title":"Mediat. Inflamm."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1016\/S0140-6736(22)00010-1","article-title":"Efficacy, durability, and safety of intravitreal faricimab up to every 16 weeks for neovascular age-related macular degeneration (TENAYA and LUCERNE): Two randomised, double-masked, phase 3, non-inferiority trials","volume":"399","author":"Heier","year":"2022","journal-title":"Lancet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1136\/bjo.2006.113902","article-title":"Non-responders to bevacizumab (Avastin) therapy of choroidal neovascular lesions","volume":"91","author":"Lux","year":"2007","journal-title":"Br. J. Ophthalmol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1021\/acschembio.7b00854","article-title":"Chemical proteomics reveals soluble epoxide hydrolase as a therapeutic target for ocular neovascularization","volume":"13","author":"Sulaiman","year":"2018","journal-title":"ACS Chem. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"95","DOI":"10.3389\/fphar.2019.00095","article-title":"Soluble epoxide hydrolase inhibition for ocular diseases: Vision for the future","volume":"10","author":"Park","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1124\/jpet.303.2.768","article-title":"Cytochrome P-450 epoxygenase metabolites of docosahexaenoate potently dilate coronary arterioles by activating large-conductance calcium-activated potassium channels","volume":"303","author":"Ye","year":"2002","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.plipres.2013.11.003","article-title":"Stabilized epoxygenated fatty acids regulate inflammation, pain, angiogenesis and cancer","volume":"53","author":"Zhang","year":"2014","journal-title":"Prog. Lipid Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"39211","DOI":"10.1038\/srep39211","article-title":"Epoxygenated fatty acids inhibit retinal vascular inflammation","volume":"6","author":"Capozzi","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.smim.2015.03.004","article-title":"The resolution code of acute inflammation: Novel pro-resolving lipid mediators in resolution","volume":"27","author":"Serhan","year":"2015","journal-title":"Semin. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"27138","DOI":"10.1074\/jbc.M501730200","article-title":"Characterization of 5,6- and 8,9-epoxyeicosatrienoic acids (5,6- and 8,9-EET) as potent in vivo angiogenic lipids","volume":"280","author":"Pozzi","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1167\/iovs.07-1087","article-title":"Role of cytochrome P450 2C epoxygenases in hypoxia-induced cell migration and angiogenesis in retinal endothelial cells","volume":"49","author":"Michaelis","year":"2008","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.1016\/j.ijcard.2012.03.167","article-title":"A potent soluble epoxide hydrolase inhibitor, t-AUCB, acts through PPARgamma to modulate the function of endothelial progenitor cells from patients with acute myocardial infarction","volume":"167","author":"Xu","year":"2013","journal-title":"Int. J. Cardiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"6530","DOI":"10.1073\/pnas.1304321110","article-title":"Epoxy metabolites of docosahexaenoic acid (DHA) inhibit angiogenesis, tumor growth, and metastasis","volume":"110","author":"Zhang","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4253","DOI":"10.1167\/iovs.14-14216","article-title":"The role of cytochrome P450 epoxygenases in retinal angiogenesis","volume":"55","author":"Capozzi","year":"2014","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"E7545","DOI":"10.1073\/pnas.1620898114","article-title":"Cytochrome P450 monooxygenase lipid metabolites are significant second messengers in the resolution of choroidal neovascularization","volume":"114","author":"Hasegawa","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1084\/jem.20131494","article-title":"Muller glia cells regulate notch signaling and retinal angiogenesis via the generation of 19,20-dihydroxydocosapentaenoic acid","volume":"211","author":"Hu","year":"2014","journal-title":"J. Exp. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/nature25013","article-title":"Inhibition of soluble epoxide hydrolase prevents diabetic retinopathy","volume":"552","author":"Hu","year":"2017","journal-title":"Nature"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"5628","DOI":"10.1074\/jbc.271.10.5628","article-title":"Apolipoprotein E is synthesized in the retina by Muller glial cells, secreted into the vitreous, and rapidly transported into the optic nerve by retinal ganglion cells","volume":"271","author":"Amaratunga","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4902","DOI":"10.1038\/s41467-019-12780-8","article-title":"Single-cell transcriptomic atlas of the human retina identifies cell types associated with age-related macular degeneration","volume":"10","author":"Menon","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.omtm.2018.01.008","article-title":"Transduction patterns of adeno-associated viral vectors in a laser-induced choroidal neovascularization mouse model","volume":"9","author":"Lee","year":"2018","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/j.bbrc.2014.03.020","article-title":"Basal and inducible anti-inflammatory epoxygenase activity in endothelial cells","volume":"446","author":"Askari","year":"2014","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1097\/SHK.0000000000000767","article-title":"Soluble epoxide hydrolase inhibitor attenuates lipopolysaccharide-induced acute lung injury and improves survival in mice","volume":"47","author":"Zhou","year":"2017","journal-title":"Shock"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.visres.2017.03.013","article-title":"M\u00fcller cells and diabetic retinopathy","volume":"139","author":"Coughlin","year":"2017","journal-title":"Vision Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1161\/ATVBAHA.113.302927","article-title":"Cytochrome P450 2C8 \u03c93-long-chain polyunsaturated fatty acid metabolites increase mouse retinal pathologic neovascularization\u2014brief report","volume":"34","author":"Shao","year":"2014","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.preteyeres.2009.12.002","article-title":"The multifunctional choroid","volume":"29","author":"Nickla","year":"2010","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1146\/annurev-pharmtox-010611-134639","article-title":"Chemical genetics\u2013based target identification in drug discovery","volume":"52","author":"Cong","year":"2012","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1038\/gt.2009.61","article-title":"Intravitreal delivery of AAV8 retinoschisin results in cell type-specific gene expression and retinal rescue in the Rs1-KO mouse","volume":"16","author":"Park","year":"2009","journal-title":"Gene Ther."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"654955","DOI":"10.3389\/fgene.2021.654955","article-title":"Transcriptome analysis of choroid and retina from tree shrew with choroidal neovascularization reveals key signaling moieties","volume":"12","author":"Jia","year":"2021","journal-title":"Front. Genet."},{"key":"ref_34","first-page":"855","article-title":"Transdifferentiated retinal pigment epithelial cells are immunoreactive for vascular endothelial growth factor in surgically excised age-related macular degeneration-related choroidal neovascular membranes","volume":"37","author":"Lopez","year":"1996","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_35","first-page":"1929","article-title":"Subfoveal fibrovascular membranes in age-related macular degeneration express vascular endothelial growth factor","volume":"37","author":"Kvanta","year":"1996","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/978-3-030-27378-1_2","article-title":"A review of pathogenic drivers of age-related macular degeneration, beyond complement, with a focus on potential endpoints for testing therapeutic interventions in preclinical studies","volume":"1185","author":"Choudhary","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.preteyeres.2017.09.001","article-title":"Complement factor H in AMD: Bridging genetic associations and pathobiology","volume":"62","author":"Toomey","year":"2018","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1016\/j.preteyeres.2009.06.001","article-title":"Para-inflammation in the aging retina","volume":"28","author":"Xu","year":"2009","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4705","DOI":"10.4049\/jimmunol.0901511","article-title":"The role of macrophage-derived IL-1 in induction and maintenance of angiogenesis","volume":"183","author":"Carmi","year":"2009","journal-title":"J. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Zhao, M., Bai, Y., Xie, W., Shi, X., Li, F., Yang, F., Sun, Y., Huang, L., and Li, X. (2015). Interleukin-1\u03b2 level is increased in vitreous of patients with neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV). PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0125150"},{"key":"ref_41","first-page":"1891","article-title":"The potential angiogenic role of macrophages in the formation of choroidal neovascular membranes","volume":"40","author":"Oh","year":"1999","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2707","DOI":"10.4049\/jimmunol.1101737","article-title":"Cutting edge: IL-6 is a marker of inflammation with no direct role in inflammasome-mediated mouse models","volume":"189","author":"McGeough","year":"2012","journal-title":"J. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/s13024-017-0175-y","article-title":"Microglia-derived IL-1\u03b2 promotes chemokine expression by M\u00fcller cells and RPE in focal retinal degeneration","volume":"12","author":"Natoli","year":"2017","journal-title":"Mol. Neurodegen."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"18084","DOI":"10.1038\/s41598-021-97522-x","article-title":"Macrophage-derived interleukin-6 is necessary and sufficient for choroidal angiogenesis","volume":"11","author":"Droho","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3098","DOI":"10.1158\/0008-5472.CAN-15-1227","article-title":"Interleukin-6 stimulates defective angiogenesis","volume":"75","author":"Gopinathan","year":"2015","journal-title":"Cancer Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1097\/IIO.0000000000000073","article-title":"Inflammatory mechanisms of age-related macular degeneration","volume":"55","author":"Knickelbein","year":"2015","journal-title":"Int. Ophthalmol. Clin."},{"key":"ref_47","first-page":"116","article-title":"TNF-\u03b1 mediates choroidal neovascularization by upregulating VEGF expression in RPE through ROS-dependent \u03b2-catenin activation","volume":"22","author":"Wang","year":"2016","journal-title":"Mol. Vis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1186\/1742-2094-7-87","article-title":"CCL2\/CCR2 and CX3CL1\/CX3CR1 chemokine axes and their possible involvement in age-related macular degeneration","volume":"7","author":"Raoul","year":"2010","journal-title":"J. Neuroinflamm."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Chen, H., Liu, B., Lukas, T.J., and Neufeld, A.H. (2008). The aged retinal pigment epithelium\/choroid: A potential substratum for the pathogenesis of age-related macular degeneration. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0002339"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2425","DOI":"10.1073\/pnas.0608167104","article-title":"Monocyte chemoattractant protein 1 mediates retinal detachment-induced photoreceptor apoptosis","volume":"104","author":"Nakazawa","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1775","DOI":"10.1167\/iovs.02-0742","article-title":"Induction of angiogenic cytokine expression in cultured RPE by ingestion of oxidized photoreceptor outer segments","volume":"44","author":"Higgins","year":"2003","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"9603","DOI":"10.1073\/pnas.1401191111","article-title":"Cytochrome P450-generated metabolites derived from \u03c9-3 fatty acids attenuate neovascularization","volume":"111","author":"Yanai","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"748361","DOI":"10.1155\/2011\/748361","article-title":"Retina and omega-3","volume":"2011","author":"Querques","year":"2011","journal-title":"J. Nutr. Metab."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2009","DOI":"10.1016\/S0022-2275(20)41904-2","article-title":"Recycling of docosahexaenoic acid in rat retinas during n-3 fatty acid deficiency","volume":"32","author":"Stinson","year":"1991","journal-title":"J. Lipid Res."},{"key":"ref_55","first-page":"91","article-title":"Dietary deficiency of N-3 fatty acids alters rhodopsin content and function in the rat retina","volume":"35","author":"Bush","year":"1994","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0009-3084(03)00101-4","article-title":"Docosahexaenoic acid: Membrane properties of a unique fatty acid","volume":"126","author":"Stillwell","year":"2003","journal-title":"Chem. Phys. Lipids"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.preteyeres.2016.12.001","article-title":"Pharmacokinetic aspects of retinal drug delivery","volume":"57","author":"Heikkinen","year":"2017","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_58","first-page":"515","article-title":"Optical coherence tomography enables imaging of tumor initiation in the TAg-RB mouse model of retinoblastoma","volume":"21","author":"Wenzel","year":"2015","journal-title":"Mol. Vis."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/0014-4835(92)90194-W","article-title":"Characterization of the interphotoreceptor matrix surrounding rod photoreceptors in the human retina","volume":"55","author":"Tien","year":"1992","journal-title":"Exp. Eye Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1016\/S0014-4835(87)80101-X","article-title":"Specialization of the interphotoreceptor matrices around cone and rod photoreceptor cells in the monkey retina, as revealed by lectin cytochemistry","volume":"45","author":"Sameshima","year":"1987","journal-title":"Exp. Eye Res."},{"key":"ref_61","first-page":"100916","article-title":"A simple method for quantitating confocal fluorescent images","volume":"25","author":"Shihan","year":"2021","journal-title":"Biochem. Biophys. Rep."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Gong, Y., Li, J., Sun, Y., Fu, Z., Liu, C.-H., Evans, L., Tian, K., Saba, N., Fredrick, T., and Morss, P. (2015). Optimization of an image-guided laser-induced choroidal neovascularization model in mice. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0132643"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1089\/jop.2015.0049","article-title":"A simple optical coherence tomography quantification method for choroidal neovascularization","volume":"31","author":"Sulaiman","year":"2015","journal-title":"J. Ocul. Pharmacol. Ther."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"493","DOI":"10.18632\/oncotarget.27380","article-title":"Calcitriol and non-calcemic vitamin D analogue, 22-oxacalcitriol, attenuate developmental and pathological choroidal vasculature angiogenesis ex vivo and in vivo","volume":"11","author":"Merrigan","year":"2020","journal-title":"Oncotarget"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"25509","DOI":"10.1038\/srep25509","article-title":"A novel small molecule ameliorates ocular neovascularisation and synergises with anti-VEGF therapy","volume":"6","author":"Sulaiman","year":"2016","journal-title":"Sci. Rep."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/24\/15595\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:36:59Z","timestamp":1760146619000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/24\/15595"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,9]]},"references-count":65,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["ijms232415595"],"URL":"https:\/\/doi.org\/10.3390\/ijms232415595","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2022,12,9]]}}}