{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T11:01:21Z","timestamp":1792494081265,"version":"4.5.0"},"reference-count":50,"publisher":"Association for Research in Vision and Ophthalmology (ARVO)","issue":"1","license":[{"start":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T00:00:00Z","timestamp":1768176000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Invest. Ophthalmol. Vis. Sci."],"published-print":{"date-parts":[[2026,1,12]]},"DOI":"10.1167\/iovs.67.1.24","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T13:30:44Z","timestamp":1768224644000},"page":"24","source":"Crossref","is-referenced-by-count":2,"title":["Silencing of lncRNA HOTAIR Using Eyedrops as a Potential Treatment for Diabetes-Associated Retinal Dysregulation and Dysfunction"],"prefix":"10.1167","volume":"67","author":[{"given":"Eric","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biao","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shali","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honglin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Ling","sequence":"additional","affiliation":[{"name":"i-RNA Corporation, London, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subrata","family":"Chakrabarti","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada"},{"name":"i-RNA Corporation, London, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"27","reference":[{"issue":"1","key":"bib1","doi-asserted-by":"crossref","first-page":"s84","DOI":"10.2337\/diacare.27.2007.S84","article-title":"Retinopathy in diabetes","volume":"27","author":"Fong","year":"2004","journal-title":"Diabetes Care"},{"issue":"11","key":"bib2","doi-asserted-by":"publisher","first-page":"1254","DOI":"10.2522\/ptj.20080020","article-title":"Epidemiology of diabetes and diabetes-related complications","volume":"88","author":"Deshpande","year":"2008","journal-title":"Phys Ther"},{"issue":"3","key":"bib3","doi-asserted-by":"publisher","first-page":"489","DOI":"10.4239\/wjd.v6.i3.489","article-title":"Diabetic retinopathy - ocular complications of diabetes mellitus","volume":"6","author":"Nentwich","year":"2015","journal-title":"World J Diabetes"},{"issue":"6","key":"bib4","doi-asserted-by":"publisher","first-page":"1816","DOI":"10.3390\/ijms19061816","article-title":"Diabetic retinopathy: pathophysiology and treatments","volume":"19","author":"Wang","year":"2018","journal-title":"Int J Mol Sci"},{"issue":"1","key":"bib5","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.mayocp.2011.10.001","article-title":"The expanding role of vascular endothelial growth factor inhibitors in ophthalmology","volume":"87","author":"Stewart","year":"2012","journal-title":"Mayo Clin Proc"},{"issue":"10","key":"bib6","doi-asserted-by":"publisher","first-page":"1275","DOI":"10.1080\/14712598.2022.2100694","article-title":"Efficacy and safety of intravitreal anti-VEGF therapy in diabetic retinopathy: what we have learned and what should we learn further?","volume":"22","author":"Uludag","year":"2022","journal-title":"Expert Opin Biol Ther"},{"issue":"5","key":"bib7","first-page":"1098","article-title":"Update on the management of diabetic retinopathy: anti-VEGF agents for the prevention of complications and progression of nonproliferative and proliferative retinopathy","volume":"13","author":"Bahr","year":"2023","journal-title":"Life (Basel)"},{"issue":"5","key":"bib8","doi-asserted-by":"publisher","first-page":"977","DOI":"10.1038\/s41433-024-03529-9","article-title":"Visual and anatomical failure of anti-VEGF therapy for retinal vascular diseases: a survival analysis of real-world data","volume":"39","author":"Fu","year":"2025","journal-title":"Eye"},{"issue":"11","key":"bib9","first-page":"1","article-title":"Angiogenic factors and cytokines in diabetic retinopathy","volume":"1","author":"Abcouwer","year":"2013","journal-title":"J Clin Cell Immunol"},{"issue":"23","key":"bib10","doi-asserted-by":"publisher","first-page":"E3030","DOI":"10.1073\/pnas.1423765112","article-title":"Angiopoietin-like 4 is a potent angiogenic factor and a novel therapeutic target for patients with proliferative diabetic retinopathy","volume":"112","author":"Babapoor-Farrokhran","year":"2015","journal-title":"Proc Natl Acad Sci USA"},{"issue":"13","key":"bib11","doi-asserted-by":"publisher","first-page":"4084","DOI":"10.1167\/iovs.19-26767","article-title":"Induced expression of VEGFC, ANGPT, and EFNB2 and their receptors characterizes neovascularization in proliferative diabetic retinopathy","volume":"60","author":"Li","year":"2019","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"3","key":"bib12","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1167\/iovs.62.3.20","article-title":"The long non-coding RNA HOTAIR is a critical epigenetic mediator of angiogenesis in diabetic retinopathy","volume":"62","author":"Biswas","year":"2021","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"1","key":"bib13","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1186\/1741-7007-11-59","article-title":"Gene regulation by the act of long non-coding RNA transcription","volume":"11","author":"Kornienko","year":"2013","journal-title":"BMC Biology"},{"issue":"2","key":"bib14","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1038\/s41580-020-00315-9","article-title":"Gene regulation by long non-coding RNAs and its biological functions","volume":"22","author":"Statello","year":"2021","journal-title":"Nat Rev Mol Cell Biol"},{"key":"bib15","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/j.jconrel.2022.01.008","article-title":"Non-viral vectors for RNA delivery","volume":"342","author":"Yan","year":"2022","journal-title":"J Control Release"},{"issue":"4","key":"bib16","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1080\/17425247.2025.2466767","article-title":"GalNac-siRNA conjugate delivery technology promotes the treatment of typical chronic liver diseases","volume":"22","author":"Qin","year":"2025","journal-title":"Expert Opin Drug Deliv"},{"issue":"12","key":"bib17","doi-asserted-by":"publisher","first-page":"e0310949","DOI":"10.1371\/journal.pone.0310949","article-title":"Differential microvascular endothelial cell responses in the retina in diabetes compared to the heart and kidneys, a spatial transcriptomic analysis","volume":"19","author":"Wang","year":"2024","journal-title":"PLoS One"},{"issue":"10","key":"bib18","doi-asserted-by":"publisher","first-page":"5423","DOI":"10.1093\/nar\/gkae350","article-title":"Evaluating the oral delivery of GalNAc-conjugated siRNAs in rodents and non-human primates","volume":"52","author":"Yu","year":"2024","journal-title":"Nucleic Acids Res"},{"issue":"1","key":"bib19","doi-asserted-by":"publisher","first-page":"bpae029","DOI":"10.1093\/biomethods\/bpae029","article-title":"A highly sensitive stem-loop RT-qPCR method to study siRNA intracellular pharmacokinetics and pharmacodynamics","volume":"9","author":"Chen","year":"2024","journal-title":"Biol Methods Protoc"},{"issue":"4","key":"bib20","doi-asserted-by":"publisher","first-page":"1314","DOI":"10.2337\/db10-1557","article-title":"MicroRNA-200b regulates vascular endothelial growth factor\u2013mediated alterations in diabetic retinopathy","volume":"60","author":"McArthur","year":"2011","journal-title":"Diabetes"},{"issue":"3","key":"bib21","doi-asserted-by":"publisher","first-page":"e0173918","DOI":"10.1371\/journal.pone.0173918","article-title":"miR-146a regulates glucose induced upregulation of inflammatory cytokines extracellular matrix proteins in the retina and kidney in diabetes","volume":"12","author":"Chen","year":"2017","journal-title":"PLoS One"},{"issue":"17","key":"bib22","doi-asserted-by":"publisher","first-page":"2419","DOI":"10.1042\/CS20200694","article-title":"Long noncoding RNA Hotair facilitates retinal endothelial cell dysfunction in diabetic retinopathy","volume":"134","author":"Zhao","year":"2020","journal-title":"Clin Sci"},{"issue":"1","key":"bib23","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1186\/s12943-023-01765-3","article-title":"HOTAIR: a potential metastatic, drug-resistant and prognostic regulator of breast cancer","volume":"22","author":"Raju","year":"2023","journal-title":"Mol Cancer"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"103141","DOI":"10.1016\/j.dnarep.2021.103141","article-title":"HOTAIR beyond repression: in protein degradation, inflammation, DNA damage response, and cell signaling","volume":"105","author":"Price","year":"2021","journal-title":"DNA Repair (Amst)"},{"issue":"37","key":"bib25","doi-asserted-by":"publisher","first-page":"e35155","DOI":"10.1097\/MD.0000000000035155","article-title":"lncRNA HOTAIR promotes ROS generation and NLRP3 inflammasome activation by inhibiting Nrf2 in diabetic retinopathy","volume":"102","author":"You","year":"2023","journal-title":"Medicine"},{"key":"bib26","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1016\/B978-1-4557-0737-9.00027-8","article-title":"Blood\u2013retinal barrier, immune privilege, and autoimmunity","author":"Katamay","year":"2013;27","journal-title":"Retina"},{"issue":"4","key":"bib27","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1016\/j.nano.2008.06.003","article-title":"Ocular nanoparticle toxicity and transfection of the retina and retinal pigment epithelium","volume":"4","author":"Prow","year":"2008","journal-title":"Nanomedicine"},{"issue":"7","key":"bib28","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1177\/0192623318792537","article-title":"The nonclinical safety profile of GalNAc-conjugated RNAi therapeutics in subacute studies","volume":"46","author":"Janas","year":"2018","journal-title":"Toxicol Pathol"},{"issue":"1","key":"bib29","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1002\/jcph.2337","article-title":"Pharmacokinetics and pharmacodynamics of GalNAc-conjugated siRNAs","volume":"64","author":"An","year":"2024","journal-title":"J Clin Pharmacol"},{"issue":"47","key":"bib30","doi-asserted-by":"publisher","first-page":"77902","DOI":"10.18632\/oncotarget.12843","article-title":"PDGF-CC underlies resistance to VEGF-A inhibition and combinatorial targeting of both suppresses pathological angiogenesis more efficiently","volume":"7","author":"Zheng","year":"2016","journal-title":"Oncotarget"},{"issue":"5","key":"bib31","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1167\/iovs.64.5.28","article-title":"Mechanisms of acquired resistance to anti-VEGF therapy for neovascular eye diseases","volume":"64","author":"Sharma","year":"2023","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"46","key":"bib32","doi-asserted-by":"publisher","first-page":"e2322759121","DOI":"10.1073\/pnas.2322759121","article-title":"VEGF inhibition increases expression of HIF-regulated angiogenic genes by the RPE limiting the response of wet AMD eyes to aflibercept","volume":"121","author":"Sharma","year":"2024","journal-title":"Proc Natl Acad Sci USA"},{"issue":"11","key":"bib33","doi-asserted-by":"publisher","first-page":"1588","DOI":"10.1016\/j.ebiom.2015.11.006","article-title":"Emerging role of VEGFC in pathological angiogenesis","volume":"2","author":"Nagai","year":"2015","journal-title":"eBioMedicine"},{"issue":"11","key":"bib34","doi-asserted-by":"publisher","first-page":"1462","DOI":"10.1093\/neuonc\/noy103","article-title":"VEGF-C sustains VEGFR2 activation under bevacizumab therapy and promotes glioblastoma maintenance","volume":"20","author":"Michaelsen","year":"2018","journal-title":"Neuro Oncol"},{"issue":"5","key":"bib35","doi-asserted-by":"publisher","first-page":"1239","DOI":"10.1007\/s00417-024-06695-4","article-title":"Emerging clinical evidence of a dual role for Ang-2 and VEGF-A blockade with faricimab in retinal diseases","volume":"263","author":"Chaudhary","year":"2025","journal-title":"Graefes Arch Clin Exp Ophthalmol"},{"key":"bib36","doi-asserted-by":"publisher","first-page":"110062","DOI":"10.1016\/j.exer.2024.110062","article-title":"VEGF-A165a and angiopoietin-2 differently affect the barrier formed by retinal endothelial cells","volume":"247","author":"Deissler","year":"2024","journal-title":"Exp Eye Res"},{"issue":"4","key":"bib37","doi-asserted-by":"publisher","first-page":"4712","DOI":"10.18632\/oncotarget.6731","article-title":"Long noncoding RNA Hotair mediated angiogenesis in nasopharyngeal carcinoma by direct and indirect signaling pathways","volume":"7","author":"Fu","year":"2015","journal-title":"Oncotarget"},{"issue":"5","key":"bib38","doi-asserted-by":"publisher","first-page":"C880","DOI":"10.1152\/ajpcell.00459.2019","article-title":"Suppression of lncRNA HOTAIR alleviates RCC angiogenesis through regulating miR-126\/EGFL7 axis","volume":"320","author":"Guo","year":"2021","journal-title":"Am J Physiol Cell Physiol"},{"issue":"1","key":"bib39","first-page":"1","article-title":"lncRNA HOTAIR mediates OGD\/R-induced cell injury and angiogenesis in a EZH2-dependent manner","volume":"23","author":"Wang","year":"2022","journal-title":"Exp Ther Med"},{"issue":"10","key":"bib40","doi-asserted-by":"publisher","first-page":"e1064","DOI":"10.1002\/iid3.1064","article-title":"LncRNA HOTAIR regulates the PI3K\/AKT pathway via the miR-126-3p\/PIK3R2 axis to participate in synovial angiogenesis in rheumatoid arthritis","volume":"11","author":"Liu","year":"2023","journal-title":"Immun Inflamm Dis"},{"issue":"1","key":"bib41","doi-asserted-by":"publisher","first-page":"108","DOI":"10.3390\/pharmaceutics13010108","article-title":"Ocular drug delivery to the retina: current innovations and future perspectives","volume":"13","author":"Kim","year":"2021","journal-title":"Pharmaceutics"},{"issue":"1","key":"bib42","doi-asserted-by":"publisher","first-page":"90","DOI":"10.3390\/pharmaceutics14010090","article-title":"Lipid Nanoparticles for the Posterior Eye Segment","volume":"14","author":"Bonilla","year":"2021","journal-title":"Pharmaceutics"},{"key":"bib43","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jconrel.2023.07.028","article-title":"Selective drug delivery to the retinal cells: biological barriers and avenues","volume":"361","author":"Ramsay","year":"2023","journal-title":"J Control Release"},{"issue":"3","key":"bib44","doi-asserted-by":"publisher","first-page":"1894","DOI":"10.1167\/iovs.14-16204","article-title":"Scleral thinning after repeated intravitreal injections of antivascular endothelial growth factor agents in the same quadrant","volume":"56","author":"Zinkernagel","year":"2015","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"6","key":"bib45","doi-asserted-by":"publisher","first-page":"1646","DOI":"10.3390\/pharmaceutics15061646","article-title":"Corneal permeability and uptake of twenty-five drugs: species comparison and quantitative structure\u2013permeability relationships","volume":"15","author":"Santana","year":"2023","journal-title":"Pharmaceutics"},{"issue":"5","key":"bib46","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1021\/acs.accounts.2c00723","article-title":"Molecular recognition of GalNAc in mucin-type O-glycosylation","volume":"56","author":"Sanz-Martinez","year":"2023","journal-title":"Acc Chem Res"},{"issue":"10","key":"bib47","doi-asserted-by":"publisher","first-page":"5423","DOI":"10.1093\/nar\/gkae350","article-title":"Evaluating the oral delivery of GalNAc-conjugated siRNAs in rodents and non-human primates","volume":"52","author":"Yu","year":"2024","journal-title":"Nucleic Acids Res"},{"issue":"20","key":"bib48","doi-asserted-by":"publisher","first-page":"4666","DOI":"10.3390\/jcm10204666","article-title":"Updates on the current treatments for diabetic retinopathy and possibility of future oral therapy","volume":"10","author":"Tomita","year":"2021","journal-title":"J Clin Med"},{"key":"bib49","doi-asserted-by":"publisher","first-page":"1347864","DOI":"10.3389\/fendo.2024.1347864","article-title":"Recent advances in the treatment and delivery system of diabetic retinopathy","volume":"15","author":"Wang","year":"2024","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"1","key":"bib50","doi-asserted-by":"publisher","first-page":"122","DOI":"10.3390\/pharmaceutics15010122","article-title":"Current treatments and innovations in diabetic retinopathy and diabetic macular edema","volume":"15","author":"Gonzalez-Cortes","year":"2023","journal-title":"Pharmaceutics"}],"container-title":["Investigative Ophthalmology & Visual Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/iovs.arvojournals.org\/article.aspx?articleid=2811352","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:32:16Z","timestamp":1791927136000},"score":1,"resource":{"primary":{"URL":"https:\/\/iovs.arvojournals.org\/article.aspx?articleid=2811352"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,12]]},"references-count":50,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1,5]]}},"URL":"https:\/\/doi.org\/10.1167\/iovs.67.1.24","relation":{},"ISSN":["1552-5783"],"issn-type":[{"value":"1552-5783","type":"print"}],"subject":[],"published":{"date-parts":[[2026,1,12]]}}}