{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T07:49:21Z","timestamp":1790668161939,"version":"4.1.0"},"reference-count":199,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:00:00Z","timestamp":1772150400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["UL1TR002378"],"award-info":[{"award-number":["UL1TR002378"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The blood\u2013retinal barrier (BRB) maintains neurovascular homeostasis by regulating solute and ion exchange between the retina and circulation. This selectivity depends on tight junctions (TJs), with claudin (Cldn) proteins forming the core structure that defines paracellular permeability. Distinct Cldn isoforms show cell-specific expression, with Cldn-5 predominating in the endothelial cells of the inner BRB and Cldn-19 is the signature Cldn in the retinal pigment epithelium forming the outer BRB. Disruption of these isoforms contributes to vascular leakage, inflammation, and neuronal loss across various ocular diseases. Cldn function in vascular homeostasis is multifaceted; barrier dysfunction does not always result from Cldn loss, as excessive expression or mislocalization, particularly of Cldn-5, can also impair BRB integrity. Cldns act as dynamic signaling hubs that respond to metabolic, oxidative, and mechanical stress and are regulated through VEGF, Wnt\/\u03b2-catenin, and RhoA\/ROCK pathways. This review summarizes current understanding of Cldn biology in retinal vascular regulation and highlights emerging therapeutic strategies aimed at stabilizing Cldn expression and junctional localization. Small molecules and blocking antibodies that enhance localization or prevent degradation are redefining barrier repair. Key questions remain regarding isoform specificity, inter-barrier communication, and systemic safety. Integrative omics and spatial imaging may reveal disease-specific Cldn signatures and guide molecular restoration of BRB integrity.<\/jats:p>","DOI":"10.3390\/cells15050417","type":"journal-article","created":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T10:41:02Z","timestamp":1772188862000},"page":"417","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Claudins in Retinal Disease: Beyond Barrier Integrity to Signaling and Therapy"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1814-4358","authenticated-orcid":false,"given":"Mohamed S.","family":"Selim","sequence":"first","affiliation":[{"name":"Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia, Augusta, GA 30912, USA"},{"name":"Department of Research, Veterans Affairs Health Care System, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8842-622X","authenticated-orcid":false,"given":"S. Priya","family":"Narayanan","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia, Augusta, GA 30912, USA"},{"name":"Department of Research, Veterans Affairs Health Care System, Augusta, GA 30912, USA"},{"name":"Vascular Biology Center, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3017-0230","authenticated-orcid":false,"given":"Payaningal R.","family":"Somanath","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia, Augusta, GA 30912, USA"},{"name":"Department of Research, Veterans Affairs Health Care System, Augusta, GA 30912, USA"},{"name":"Vascular Biology Center, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1007\/978-1-60761-938-3_5","article-title":"The blood-retinal barrier: Structure and functional significance","volume":"686","author":"Runkle","year":"2011","journal-title":"Methods Mol. Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.neuron.2012.10.002","article-title":"The neuronal organization of the retina","volume":"76","author":"Masland","year":"2012","journal-title":"Neuron"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.preteyeres.2006.05.003","article-title":"Muller cells in the healthy and diseased retina","volume":"25","author":"Bringmann","year":"2006","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"105115","DOI":"10.1016\/j.phrs.2020.105115","article-title":"Regulation of blood-retinal barrier cell-junctions in diabetic retinopathy","volume":"161","author":"Rudraraju","year":"2020","journal-title":"Pharmacol. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1007\/978-1-4614-4711-5_3","article-title":"The blood-retina barrier: Tight junctions and barrier modulation","volume":"763","author":"Campbell","year":"2012","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1848212","DOI":"10.1080\/21688370.2020.1848212","article-title":"Cell-cell junctions: Structure and regulation in physiology and pathology","volume":"9","author":"Adil","year":"2021","journal-title":"Tissue Barriers"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Selim, M.S., Matani, B.R., Henry-Ojo, H.O., Narayanan, S.P., and Somanath, P.R. (2025). Claudin 5 Across the Vascular Landscape: From Blood-Tissue Barrier Regulation to Disease Mechanisms. Cells, 14.","DOI":"10.3390\/cells14171346"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1038\/35067088","article-title":"Multifunctional strands in tight junctions","volume":"2","author":"Tsukita","year":"2001","journal-title":"Nat. Rev. Mol. Cell. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/j.bbamem.2007.10.018","article-title":"Structure and function of claudins","volume":"1778","author":"Krause","year":"2008","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.tibs.2018.09.008","article-title":"The Claudins: From Tight Junctions to Biological Systems","volume":"44","author":"Tsukita","year":"2019","journal-title":"Trends Biochem. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1002\/jcp.24523","article-title":"Kruppel-like factor 4 regulates blood-tumor barrier permeability via ZO-1, occludin and claudin-5","volume":"229","author":"Ma","year":"2014","journal-title":"J. Cell. Physiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"L40","DOI":"10.1152\/ajplung.00299.2010","article-title":"Differential effects of claudin-3 and claudin-4 on alveolar epithelial barrier function","volume":"301","author":"Mitchell","year":"2011","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1111\/j.1749-6632.2012.06545.x","article-title":"Roles for claudins in alveolar epithelial barrier function","volume":"1257","author":"Overgaard","year":"2012","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.semcdb.2015.04.009","article-title":"Claudins: Gatekeepers of lung epithelial function","volume":"42","author":"Schlingmann","year":"2015","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.phrs.2019.01.006","article-title":"Endothelial stromelysin1 regulation by the forkhead box-O transcription factors is crucial in the exudative phase of acute lung injury","volume":"141","author":"Artham","year":"2019","journal-title":"Pharmacol. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1464","DOI":"10.1038\/s41416-018-0110-1","article-title":"Endothelial Akt1 loss promotes prostate cancer metastasis via beta-catenin-regulated tight-junction protein turnover","volume":"118","author":"Gao","year":"2018","journal-title":"Br. J. Cancer"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3917","DOI":"10.1007\/s00018-016-2232-z","article-title":"Akt1 promotes stimuli-induced endothelial-barrier protection through FoxO-mediated tight-junction protein turnover","volume":"73","author":"Gao","year":"2016","journal-title":"Cell. Mol. Life Sci. CMLS"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2599","DOI":"10.1002\/jcp.25791","article-title":"Modulation of long-term endothelial-barrier integrity is conditional to the cross-talk between Akt and Src signaling","volume":"232","author":"Gao","year":"2017","journal-title":"J. Cell. Physiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1038\/ncb1752","article-title":"Endothelial adherens junctions control tight junctions by VE-cadherin-mediated upregulation of claudin-5","volume":"10","author":"Taddei","year":"2008","journal-title":"Nat. Cell Biol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Rudraraju, M., Shan, S., Liu, F., Tyler, J., Caldwell, R.B., Somanath, P.R., and Narayanan, S.P. (2023). Pharmacological Modulation of beta-Catenin Preserves Endothelial Barrier Integrity and Mitigates Retinal Vascular Permeability and Inflammation. J. Clin. Med., 12.","DOI":"10.3390\/jcm12227145"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Rudraraju, M., Narayanan, S.P., and Somanath, P.R. (2021). Distinct Mechanisms of Human Retinal Endothelial Barrier Modulation In Vitro by Mediators of Diabetes and Uveitis. Life, 12.","DOI":"10.3390\/life12010033"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"114714","DOI":"10.1016\/j.biopha.2023.114714","article-title":"Triciribine attenuates pathological neovascularization and vascular permeability in a mouse model of proliferative retinopathy","volume":"162","author":"Shan","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1977","DOI":"10.1073\/pnas.0808698106","article-title":"VEGF-mediated disruption of endothelial CLN-5 promotes blood-brain barrier breakdown","volume":"106","author":"Argaw","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1186\/s12974-024-03190-9","article-title":"Suppression of inner blood-retinal barrier breakdown and pathogenic Muller glia activation in ischemia retinopathy by myeloid cell depletion","volume":"21","author":"Zhou","year":"2024","journal-title":"J. Neuroinflamm."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e13270","DOI":"10.1111\/bpa.13270","article-title":"Decreased microvascular claudin-5 levels in cerebral amyloid angiopathy associated with intracerebral haemorrhage","volume":"34","author":"Jakel","year":"2024","journal-title":"Brain Pathol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1152\/physrev.00019.2012","article-title":"Claudins and the modulation of tight junction permeability","volume":"93","author":"Gunzel","year":"2013","journal-title":"Physiol. Rev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1126\/science.1248571","article-title":"Crystal structure of a claudin provides insight into the architecture of tight junctions","volume":"344","author":"Suzuki","year":"2014","journal-title":"Science"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1186\/gb-2009-10-8-235","article-title":"The claudins","volume":"10","author":"Morin","year":"2009","journal-title":"Genome Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.margen.2013.05.001","article-title":"Phylogenetic revision of the claudin gene family","volume":"11","author":"Baltzegar","year":"2013","journal-title":"Mar. Genom."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1007\/s00726-025-03479-w","article-title":"Exploring claudin proteins: From sequence motifs to their impact on tight junction-mediated signaling pathways","volume":"57","author":"Bao","year":"2025","journal-title":"Amino Acids"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.semcdb.2014.08.011","article-title":"Architecture of tight junctions and principles of molecular composition","volume":"36","author":"Anderson","year":"2014","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1096\/fj.07-8319com","article-title":"Formation of tight junction: Determinants of homophilic interaction between classic claudins","volume":"22","author":"Piontek","year":"2008","journal-title":"FASEB J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1074\/jbc.M109005200","article-title":"Multi-PDZ domain protein 1 (MUPP1) is concentrated at tight junctions through its possible interaction with claudin-1 and junctional adhesion molecule","volume":"277","author":"Hamazaki","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"8408","DOI":"10.1128\/MCB.24.19.8408-8417.2004","article-title":"Selective decrease in paracellular conductance of tight junctions: Role of the first extracellular domain of claudin-5","volume":"24","author":"Wen","year":"2004","journal-title":"Mol. Cell. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"5109","DOI":"10.1242\/jcs.02631","article-title":"Paracellin-1 and the modulation of ion selectivity of tight junctions","volume":"118","author":"Hou","year":"2005","journal-title":"J. Cell Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1146\/annurev-physiol-012110-142150","article-title":"Tight junction pore and leak pathways: A dynamic duo","volume":"73","author":"Shen","year":"2011","journal-title":"Annu. Rev. Physiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"a002584","DOI":"10.1101\/cshperspect.a002584","article-title":"Physiology and function of the tight junction","volume":"1","author":"Anderson","year":"2009","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"C1213","DOI":"10.1152\/ajpcell.00558.2003","article-title":"The tight junction: A multifunctional complex","volume":"286","author":"Schneeberger","year":"2004","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.yexcr.2003.12.014","article-title":"Thr203 of claudin-1, a putative phosphorylation site for MAP kinase, is required to promote the barrier function of tight junctions","volume":"295","author":"Fujibe","year":"2004","journal-title":"Exp. Cell Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1242\/jcs.01735","article-title":"Palmitoylation of claudins is required for efficient tight-junction localization","volume":"118","author":"Gambling","year":"2005","journal-title":"J. Cell Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"469","DOI":"10.3727\/096504001108747477","article-title":"Involvement of claudin-1 in the beta-catenin\/Tcf signaling pathway and its frequent upregulation in human colorectal cancers","volume":"12","author":"Miwa","year":"2001","journal-title":"Oncol. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1083\/jcb.200110122","article-title":"Claudin-based tight junctions are crucial for the mammalian epidermal barrier: A lesson from claudin-1-deficient mice","volume":"156","author":"Furuse","year":"2002","journal-title":"J. Cell Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"L1166","DOI":"10.1152\/ajplung.00182.2003","article-title":"Role of claudin interactions in airway tight junctional permeability","volume":"285","author":"Coyne","year":"2003","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"7380","DOI":"10.1128\/MCB.21.21.7380-7390.2001","article-title":"claudin-18, a novel downstream target gene for the T\/EBP\/NKX2.1 homeodomain transcription factor, encodes lung- and stomach-specific isoforms through alternative splicing","volume":"21","author":"Niimi","year":"2001","journal-title":"Mol. Cell. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1086\/508617","article-title":"Mutations in the tight-junction gene claudin 19 (CLDN19) are associated with renal magnesium wasting, renal failure, and severe ocular involvement","volume":"79","author":"Konrad","year":"2006","journal-title":"Am. J. Hum. Genet."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1111\/apha.12742","article-title":"Claudin-2-mediated cation and water transport share a common pore","volume":"219","author":"Rosenthal","year":"2017","journal-title":"Acta Physiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1111\/j.1749-6632.2009.04051.x","article-title":"Claudin function in the thick ascending limb of Henle\u2019s loop","volume":"1165","author":"Gunzel","year":"2009","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1111\/j.1749-6632.2012.06529.x","article-title":"The yin and yang of claudin-14 function in human diseases","volume":"1258","author":"Hou","year":"2012","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1002\/humu.20172","article-title":"Different mechanisms preclude mutant CLDN14 proteins from forming tight junctions In Vitro","volume":"25","author":"Wattenhofer","year":"2005","journal-title":"Hum. Mutat."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2049","DOI":"10.1093\/hmg\/ddg210","article-title":"Claudin 14 knockout mice, a model for autosomal recessive deafness DFNB29, are deaf due to cochlear hair cell degeneration","volume":"12","author":"Belyantseva","year":"2003","journal-title":"Hum. Mol. Genet."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1002\/ajmg.a.34407","article-title":"Novel CLDN14 mutations in Pakistani families with autosomal recessive non-syndromic hearing loss","volume":"158A","author":"Lee","year":"2012","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1083\/jcb.200302070","article-title":"Size-selective loosening of the blood-brain barrier in claudin-5-deficient mice","volume":"161","author":"Nitta","year":"2003","journal-title":"J. Cell Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2051","DOI":"10.1002\/jnr.24040","article-title":"Claudin domain containing 1 contributing to endothelial cell adhesion decreases in presence of cerebellar hemorrhage","volume":"95","author":"Ohnishi","year":"2017","journal-title":"J. Neurosci. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3798","DOI":"10.1038\/s41598-018-22047-9","article-title":"Absence of Claudin 11 in CNS Myelin Perturbs Behavior and Neurotransmitter Levels in Mice","volume":"8","author":"Maheras","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Adil, M.S., Parvathagiri, V., Verma, A., Liu, F., Rudraraju, M., Narayanan, S.P., and Somanath, P.R. (2022). Claudin-17 Deficiency in Mice Results in Kidney Injury Due to Electrolyte Imbalance and Oxidative Stress. Cells, 11.","DOI":"10.3390\/cells11111782"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Adil, M.S., Parvathagiri, V., Alanazi, A.H., Khulood, D., Narayanan, S.P., and Somanath, P.R. (2025). Claudin-17 Deficiency Drives Vascular Permeability and Inflammation Causing Lung Injury. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26083612"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"7556","DOI":"10.1167\/iovs.11-7185","article-title":"Differential expression of claudins in retinas during normal development and the angiogenesis of oxygen-induced retinopathy","volume":"52","author":"Luo","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Daneman, R., Zhou, L., Agalliu, D., Cahoy, J.D., Kaushal, A., and Barres, B.A. (2010). The mouse blood-brain barrier transcriptome: A new resource for understanding the development and function of brain endothelial cells. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0013741"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1038\/s42003-019-0355-0","article-title":"Disease-associated mutations of claudin-19 disrupt retinal neurogenesis and visual function","volume":"2","author":"Wang","year":"2019","journal-title":"Commun. Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1710","DOI":"10.1016\/j.fmre.2023.08.011","article-title":"The retinal pigment epithelium: Functions and roles in ocular diseases","volume":"4","author":"Wang","year":"2024","journal-title":"Fundam. Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1167\/iovs.02-0473","article-title":"Apical and basal regulation of the permeability of the retinal pigment epithelium","volume":"44","author":"Peng","year":"2003","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"100846","DOI":"10.1016\/j.preteyeres.2020.100846","article-title":"The cell biology of the retinal pigment epithelium","volume":"78","author":"Lakkaraju","year":"2020","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"5468","DOI":"10.1073\/pnas.1709211115","article-title":"Defective phagosome motility and degradation in cell nonautonomous RPE pathogenesis of a dominant macular degeneration","volume":"115","author":"Hazim","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1167\/iovs.62.2.14","article-title":"Knockdown of Claudin-19 in the Retinal Pigment Epithelium Is Accompanied by Slowed Phagocytosis and Increased Expression of SQSTM1","volume":"62","author":"Liu","year":"2021","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"108157","DOI":"10.1016\/j.exer.2020.108157","article-title":"Claudins regulate gene and protein expression of the retinal pigment epithelium independent of their association with tight junctions","volume":"198","author":"Liu","year":"2020","journal-title":"Exp. Eye Res."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Naylor, A., Hopkins, A., Hudson, N., and Campbell, M. (2019). Tight Junctions of the Outer Blood Retina Barrier. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21010211"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Nakai, A., Lee, D., Zhang, Y., Shoda, C., Imanishi, T., Jeong, H., Ikeda, S.-i., Negishi, K., Nakashizuka, H., and Yamagami, S. (2023). Tight junction component protein claudin-1 deficiency in retinal pigment epithelium leads to early and intermediate age-related macular degeneration phenotypes in mice. bioRxiv.","DOI":"10.1101\/2023.12.07.570525"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1167\/iovs.10-5984","article-title":"Claudin-19 and the barrier properties of the human retinal pigment epithelium","volume":"52","author":"Peng","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.exer.2013.07.018","article-title":"VEGF but not PlGF disturbs the barrier of retinal endothelial cells","volume":"115","author":"Deissler","year":"2013","journal-title":"Exp. Eye Res."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Hudson, N., and Campbell, M. (2021). Tight Junctions of the Neurovascular Unit. Front. Mol. Neurosci., 14.","DOI":"10.3389\/fnmol.2021.752781"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/nrn1824","article-title":"Astrocyte-endothelial interactions at the blood-brain barrier","volume":"7","author":"Abbott","year":"2006","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_72","first-page":"305","article-title":"Claudin-17 loss Compromises Blood-Retinal Barrier Integrity: Implications for Ischemic Retinopathies","volume":"65","author":"Shenoy","year":"2024","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Medina-Arellano, A.E., Albert-Garay, J.S., Medina-Sanchez, T., Fonseca, K.H., Ruiz-Cruz, M., and Ochoa-de la Paz, L. (2024). Muller cells and retinal angiogenesis: Critical regulators in health and disease. Front. Cell. Neurosci., 18.","DOI":"10.3389\/fncel.2024.1513686"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Garcia-Pradas, L., Gleiser, C., Wizenmann, A., Wolburg, H., and Mack, A.F. (2018). Glial Cells in the Fish Retinal Nerve Fiber Layer Form Tight Junctions, Separating and Surrounding Axons. Front. Mol. Neurosci., 11.","DOI":"10.3389\/fnmol.2018.00367"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.2174\/1566524014666141015160355","article-title":"The effect of claudin-5 overexpression on the interactions of claudin-1 and -2 and barrier function in retinal cells","volume":"14","author":"Tian","year":"2014","journal-title":"Curr. Mol. Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1111\/ejn.13965","article-title":"A journey into the retina: Muller glia commanding survival and death","volume":"47","author":"Subirada","year":"2018","journal-title":"Eur. J. Neurosci."},{"key":"ref_77","first-page":"183","article-title":"The outer limiting membrane (OLM) revisited: Clinical implications","volume":"4","author":"Omri","year":"2010","journal-title":"Clin. Ophthalmol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.visres.2017.05.009","article-title":"The inner blood-retinal barrier: Cellular basis and development","volume":"139","author":"Ramos","year":"2017","journal-title":"Vis. Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"e24782","DOI":"10.4161\/tisb.24782","article-title":"Regulation of claudins in blood-tissue barriers under physiological and pathological states","volume":"1","author":"Goncalves","year":"2013","journal-title":"Tissue Barriers"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2307","DOI":"10.1038\/s41467-025-57625-9","article-title":"Spatiotemporally resolved transcriptomics reveals the cellular dynamics of human retinal development","volume":"16","author":"Zhang","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1167\/iovs.06-0723","article-title":"Gene expression profiling of zebrafish embryonic retinal pigment epithelium In Vivo","volume":"48","author":"Leung","year":"2007","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"3825","DOI":"10.1172\/JCI76431","article-title":"Canonical WNT signaling components in vascular development and barrier formation","volume":"124","author":"Zhou","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1038\/ng957","article-title":"Mutant frizzled-4 disrupts retinal angiogenesis in familial exudative vitreoretinopathy","volume":"32","author":"Robitaille","year":"2002","journal-title":"Nat. Genet."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.molmed.2010.07.003","article-title":"The Norrin\/Frizzled4 signaling pathway in retinal vascular development and disease","volume":"16","author":"Ye","year":"2010","journal-title":"Trends Mol. Med."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1016\/j.cell.2012.10.042","article-title":"Norrin\/Frizzled4 signaling in retinal vascular development and blood brain barrier plasticity","volume":"151","author":"Wang","year":"2012","journal-title":"Cell"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"e130273","DOI":"10.1172\/jci.insight.130273","article-title":"Dysregulated claudin-5 cycling in the inner retina causes retinal pigment epithelial cell atrophy","volume":"4","author":"Hudson","year":"2019","journal-title":"JCI Insight"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.3109\/10715762.2011.595408","article-title":"Endoplasmic reticulum stress induces retinal endothelial permeability of extracellular-superoxide dismutase","volume":"45","author":"Adachi","year":"2011","journal-title":"Free Radic. Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.3109\/02713683.2011.606592","article-title":"Increased expression of tight junctions in ARPE-19 cells under endoplasmic reticulum stress","volume":"36","author":"Yoshikawa","year":"2011","journal-title":"Curr. Eye Res."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Wang, W., and Lo, A.C.Y. (2018). Diabetic Retinopathy: Pathophysiology and Treatments. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19061816"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"109119","DOI":"10.1016\/j.diabres.2021.109119","article-title":"IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045","volume":"183","author":"Sun","year":"2022","journal-title":"Diabetes Res. Clin. Pr."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1016\/j.ophtha.2021.04.027","article-title":"Global Prevalence of Diabetic Retinopathy and Projection of Burden through 2045: Systematic Review and Meta-analysis","volume":"128","author":"Teo","year":"2021","journal-title":"Ophthalmology"},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Shaukat, N., Amin, J., Sharif, M.I., Sharif, M.I., Kadry, S., and Sevcik, L. (2023). Classification and Segmentation of Diabetic Retinopathy: A Systemic Review. Appl. Sci., 13.","DOI":"10.3390\/app13053108"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/S0278-5846(03)00023-X","article-title":"A new view of diabetic retinopathy: A neurodegenerative disease of the eye","volume":"27","author":"Barber","year":"2003","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"ref_94","first-page":"1953","article-title":"Vascular permeability in experimental diabetes is associated with reduced endothelial occludin content: Vascular endothelial growth factor decreases occludin in retinal endothelial cells","volume":"47","author":"Antonetti","year":"1998","journal-title":"Penn State Retina Research Group. Diabetes"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.preteyeres.2013.02.001","article-title":"Molecular basis of the inner blood-retinal barrier and its breakdown in diabetic macular edema and other pathological conditions","volume":"34","author":"Klaassen","year":"2013","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Early Treatment Diabetic Retinopathy Study Research Group (1991). Early Treatment Diabetic Retinopathy Study design and baseline patient characteristics. Ophthalmology, 98, 741\u2013756.","DOI":"10.1016\/S0161-6420(13)38009-9"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.1016\/j.ophtha.2013.02.034","article-title":"Long-term outcomes of ranibizumab therapy for diabetic macular edema: The 36-month results from two phase III trials: RISE and RIDE","volume":"120","author":"Brown","year":"2013","journal-title":"Ophthalmology"},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Diabetic Retinopathy Clinical Research Network (2008). A randomized trial comparing intravitreal triamcinolone acetonide and focal\/grid photocoagulation for diabetic macular edema. Ophthalmology, 115, 1447\u20131459.e10.","DOI":"10.1016\/j.ophtha.2008.06.015"},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"DRUS Research Group (1990). Early vitrectomy for severe vitreous hemorrhage in diabetic retinopathy. Four-year results of a randomized trial: Diabetic Retinopathy Vitrectomy Study Report 5. Arch. Ophthalmol., 108, 958\u2013964.","DOI":"10.1001\/archopht.1990.01070090060040"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1007\/978-1-4419-1399-9_34","article-title":"Reversible and size-selective opening of the inner Blood-Retina barrier: A novel therapeutic strategy","volume":"664","author":"Campbell","year":"2010","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"19854","DOI":"10.1073\/pnas.1911532117","article-title":"Inducers of the endothelial cell barrier identified through chemogenomic screening in genome-edited hPSC-endothelial cells","volume":"117","author":"Roudnicky","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.jconrel.2021.06.009","article-title":"Safety and efficacy of an anti-claudin-5 monoclonal antibody to increase blood-brain barrier permeability for drug delivery to the brain in a non-human primate","volume":"336","author":"Tachibana","year":"2021","journal-title":"J. Control Release"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1167\/iovs.15-18658","article-title":"FTY720 Attenuates Retinal Inflammation and Protects Blood-Retinal Barrier in Diabetic Rats","volume":"57","author":"Fan","year":"2016","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"2386183","DOI":"10.1080\/21688370.2024.2386183","article-title":"The impact of diabetes mellitus on blood-tissue barrier regulation and vascular complications: Is the lung different from other organs?","volume":"13","author":"Alanazi","year":"2025","journal-title":"Tissue Barriers"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"801269","DOI":"10.1155\/2014\/801269","article-title":"Molecular mechanisms of diabetic retinopathy, general preventive strategies, and novel therapeutic targets","volume":"2014","author":"Safi","year":"2014","journal-title":"BioMed Res. Int."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.2337\/diabetes.54.6.1615","article-title":"The pathobiology of diabetic complications: A unifying mechanism","volume":"54","author":"Brownlee","year":"2005","journal-title":"Diabetes"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.exer.2014.02.016","article-title":"The effect of hyperglycaemia on permeability and the expression of junctional complex molecules in human retinal and choroidal endothelial cells","volume":"121","author":"Saker","year":"2014","journal-title":"Exp. Eye Res."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.exer.2009.01.006","article-title":"Altered expression of genes related to blood-retina barrier disruption in streptozotocin-induced diabetes","volume":"89","author":"Klaassen","year":"2009","journal-title":"Exp. Eye Res."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"5267","DOI":"10.1210\/en.2010-0571","article-title":"C1q\/TNF-related protein-3 represents a novel and endogenous lipopolysaccharide antagonist of the adipose tissue","volume":"151","author":"Kopp","year":"2010","journal-title":"Endocrinology"},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Yan, Z., Zhao, J., Gan, L., Zhang, Y., Guo, R., Cao, X., Lau, W.B., Ma, X., and Wang, Y. (2017). CTRP3 is a novel biomarker for diabetic retinopathy and inhibits HGHL-induced VCAM-1 expression in an AMPK-dependent manner. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0178253"},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Yan, Z., Wang, C., Meng, Z., Gan, L., Guo, R., Liu, J., Bond Lau, W., Xie, D., Zhao, J., and Lopez, B.L. (2022). C1q\/TNF-Related Protein 3 Prevents Diabetic Retinopathy via AMPK-Dependent Stabilization of Blood-Retinal Barrier Tight Junctions. Cells, 11.","DOI":"10.3390\/cells11050779"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1016\/j.bbagen.2009.04.016","article-title":"The role of advanced glycation end products in retinal ageing and disease","volume":"1790","author":"Glenn","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"2826","DOI":"10.2337\/diabetes.51.9.2826","article-title":"The AGE inhibitor pyridoxamine inhibits development of retinopathy in experimental diabetes","volume":"51","author":"Stitt","year":"2002","journal-title":"Diabetes"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"11555","DOI":"10.1073\/pnas.88.24.11555","article-title":"Aminoguanidine treatment inhibits the development of experimental diabetic retinopathy","volume":"88","author":"Hammes","year":"1991","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1159\/000075627","article-title":"Randomized trial of an inhibitor of formation of advanced glycation end products in diabetic nephropathy","volume":"24","author":"Bolton","year":"2004","journal-title":"Am. J. Nephrol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.exer.2013.02.012","article-title":"TNF-alpha disrupts morphologic and functional barrier properties of polarized retinal pigment epithelium","volume":"110","author":"Shirasawa","year":"2013","journal-title":"Exp. Eye Res."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.exer.2018.09.009","article-title":"Inhibition of interleukin-6 trans-signaling prevents inflammation and endothelial barrier disruption in retinal endothelial cells","volume":"178","author":"Valle","year":"2019","journal-title":"Exp. Eye Res."},{"key":"ref_118","first-page":"3974","article-title":"Mechanisms of retinal and choroidal neovascularization","volume":"35","year":"1994","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.2353\/ajpath.2007.060693","article-title":"Hypoxia disrupts the barrier function of neural blood vessels through changes in the expression of claudin-5 in endothelial cells","volume":"170","author":"Koto","year":"2007","journal-title":"Am. J. Pathol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1186\/s12964-022-00976-3","article-title":"Caveolin-1 accelerates hypoxia-induced endothelial dysfunction in high-altitude cerebral edema","volume":"20","author":"Xue","year":"2022","journal-title":"Cell Commun. Signal"},{"key":"ref_121","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_122","doi-asserted-by":"crossref","unstructured":"Deissler, H.L., Rehak, M., and Wolf, A. (2022). Impairment of the Retinal Endothelial Cell Barrier Induced by Long-Term Treatment with VEGF-A(165) No Longer Depends on the Growth Factor\u2019s Presence. Biomolecules, 12.","DOI":"10.3390\/biom12050734"},{"key":"ref_123","first-page":"a006411","article-title":"Antiangiogenic therapy for ischemic retinopathies","volume":"2","author":"Silva","year":"2012","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"2347070","DOI":"10.1080\/21688370.2024.2347070","article-title":"Spermine oxidase inhibitor, MDL 72527, reduced neovascularization, vascular permeability, and acrolein-conjugated proteins in a mouse model of ischemic retinopathy","volume":"13","author":"Alhumaid","year":"2025","journal-title":"Tissue Barriers"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.7150\/thno.92463","article-title":"Emerging role of extracellular vesicles in diabetic retinopathy","volume":"14","author":"Zhu","year":"2024","journal-title":"Theranostics"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/nrm.2017.125","article-title":"Shedding light on the cell biology of extracellular vesicles","volume":"19","author":"Raposo","year":"2018","journal-title":"Nat. Rev. Mol. Cell. Biol."},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Shan, S., Alanazi, A.H., Han, Y., Zhang, D., Liu, Y., Narayanan, S.P., and Somanath, P.R. (2024). Pro-Inflammatory Characteristics of Extracellular Vesicles in the Vitreous of Type 2 Diabetic Patients. Biomedicines, 12.","DOI":"10.3390\/biomedicines12092053"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.2337\/db17-1587","article-title":"Plasma Exosomes Contribute to Microvascular Damage in Diabetic Retinopathy by Activating the Classical Complement Pathway","volume":"67","author":"Huang","year":"2018","journal-title":"Diabetes"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1007\/s12177-011-9068-4","article-title":"RPE barrier breakdown in diabetic retinopathy: Seeing is believing","volume":"4","author":"Xu","year":"2011","journal-title":"J. Ocul. Biol. Dis. Infor"},{"key":"ref_130","first-page":"1836","article-title":"Role of Claudin 19 in the Breakdown of the Outer Blood Retinal Barrier in Diabetic Retinopathy","volume":"64","author":"Hernandez","year":"2023","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"2160","DOI":"10.1167\/iovs.10-6518","article-title":"Significance of outer blood-retina barrier breakdown in diabetes and ischemia","volume":"52","author":"Xu","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_132","first-page":"875","article-title":"Insulin-induced early worsening in diabetic retinopathy is mediated via disruption of claudin-19 tight junctions in the RPE","volume":"65","author":"Hernandez","year":"2024","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.jprot.2012.07.014","article-title":"Effect of high glucose on secreted proteome in cultured retinal pigmented epithelium cells: Its possible relevance to clinical diabetic retinopathy","volume":"77","author":"Chen","year":"2012","journal-title":"J. Proteom."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.semcdb.2014.09.002","article-title":"Tight junction, selective permeability, and related diseases","volume":"36","author":"Krug","year":"2014","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1001\/jama.2023.26074","article-title":"Age-Related Macular Degeneration: A Review","volume":"331","author":"Fleckenstein","year":"2024","journal-title":"JAMA"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/j.mcna.2021.01.003","article-title":"Age-Related Macular Degeneration","volume":"105","author":"Thomas","year":"2021","journal-title":"Med. Clin. N. Am."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1021\/acsnano.2c05824","article-title":"Highly Retina-Permeating and Long-Acting Resveratrol\/Metformin Nanotherapeutics for Enhanced Treatment of Macular Degeneration","volume":"17","author":"Nguyen","year":"2023","journal-title":"ACS Nano"},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"Tisi, A., Feligioni, M., Passacantando, M., Ciancaglini, M., and Maccarone, R. (2021). The Impact of Oxidative Stress on Blood-Retinal Barrier Physiology in Age-Related Macular Degeneration. Cells, 10.","DOI":"10.3390\/cells10010064"},{"key":"ref_139","doi-asserted-by":"crossref","unstructured":"Shu, D.Y., Butcher, E., and Saint-Geniez, M. (2020). EMT and EndMT: Emerging Roles in Age-Related Macular Degeneration. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21124271"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"802","DOI":"10.2174\/156652410793937813","article-title":"The retinal pigment epithelium in health and disease","volume":"10","author":"Sparrow","year":"2010","journal-title":"Curr. Mol. Med."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1186\/s13073-015-0183-x","article-title":"Restoration of mesenchymal retinal pigmented epithelial cells by TGFbeta pathway inhibitors: Implications for age-related macular degeneration","volume":"7","author":"Radeke","year":"2015","journal-title":"Genome Med."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.ophtha.2017.08.038","article-title":"The Progression of Geographic Atrophy Secondary to Age-Related Macular Degeneration","volume":"125","author":"Fleckenstein","year":"2018","journal-title":"Ophthalmology"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"5016","DOI":"10.1167\/iovs.11-8311","article-title":"Effects of proinflammatory cytokines on the claudin-19 rich tight junctions of human retinal pigment epithelium","volume":"53","author":"Peng","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_144","first-page":"0710","article-title":"Retinal detachment","volume":"2014","author":"Steel","year":"2014","journal-title":"BMJ Clin. Evid."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/S0733-8627(20)30580-0","article-title":"Blunt ocular trauma","volume":"6","author":"Joondeph","year":"1988","journal-title":"Emerg. Med. Clin. N. Am."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1016\/j.preteyeres.2008.09.003","article-title":"Blood-retinal barrier in hypoxic ischaemic conditions: Basic concepts, clinical features and management","volume":"27","author":"Kaur","year":"2008","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_147","unstructured":"Blair, K., and Czyz, C.N. (2025). Retinal Detachment. StatPearls, StatPearls Publishing LLC."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"7018","DOI":"10.1038\/s41598-022-11062-6","article-title":"Rhegmatogenous retinal detachment induces more severe macular capillary changes than central serous chorioretinopathy","volume":"12","author":"Lee","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1159\/000509157","article-title":"Nonperfused Peripheral Retinal Area in Eyes with Chronic Rhegmatogenous Retinal Detachment","volume":"11","author":"Tatsumi","year":"2020","journal-title":"Case Rep. Ophthalmol."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"9989","DOI":"10.1073\/pnas.1820387116","article-title":"Retinal microglia initiate neuroinflammation in ocular autoimmunity","volume":"116","author":"Okunuki","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/0002-9394(69)90016-6","article-title":"Experimental Retinal Detachment in the Owl Monkey: V. Electron Microscopy of the Reattached Retina","volume":"67","author":"Kroll","year":"1969","journal-title":"Am. J. Ophthalmol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1038\/sj.eye.6700202","article-title":"Animal models of retinal detachment and reattachment: Identifying cellular events that may affect visual recovery","volume":"16","author":"Lewis","year":"2002","journal-title":"Eye"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1097\/IIO.0000000000000495","article-title":"Proliferative Vitreoretinopathy: Pathophysiology and Therapeutic Approaches","volume":"64","author":"Lin","year":"2024","journal-title":"Int. Ophthalmol. Clin."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.preteyeres.2011.06.002","article-title":"Integration of tight junctions and claudins with the barrier functions of the retinal pigment epithelium","volume":"30","author":"Rizzolo","year":"2011","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_155","doi-asserted-by":"crossref","unstructured":"Delyfer, M.N., Raffelsberger, W., Mercier, D., Korobelnik, J.F., Gaudric, A., Charteris, D.G., Tadayoni, R., Metge, F., Caputo, G., and Barale, P.O. (2011). Transcriptomic analysis of human retinal detachment reveals both inflammatory response and photoreceptor death. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0028791"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1136\/bjo.2005.081224","article-title":"The number of people with glaucoma worldwide in 2010 and 2020","volume":"90","author":"Quigley","year":"2006","journal-title":"Br. J. Ophthalmol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1212\/cont.0000000000001545","article-title":"Optic Neuropathies","volume":"31","year":"2025","journal-title":"Continuum"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.1016\/j.ophtha.2014.05.013","article-title":"Global prevalence of glaucoma and projections of glaucoma burden through 2040: A systematic review and meta-analysis","volume":"121","author":"Tham","year":"2014","journal-title":"Ophthalmology"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.1001\/jama.2014.3192","article-title":"The pathophysiology and treatment of glaucoma: A review","volume":"311","author":"Weinreb","year":"2014","journal-title":"JAMA"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1006\/exer.1996.0184","article-title":"A rat model of chronic pressure-induced optic nerve damage","volume":"64","author":"Morrison","year":"1997","journal-title":"Exp. Eye Res."},{"key":"ref_161","doi-asserted-by":"crossref","unstructured":"Zhang, C., Sim\u00f3n, M., Lim, H., Tolman, N.G., Horbal, L., Juarez, F.A., Bhandari, A., Montgomery, C., and John, S.W.M. (2024). IOP-induced blood-retinal barrier compromise contributes to RGC death in glaucoma. bioRxiv.","DOI":"10.1101\/2024.10.15.618539"},{"key":"ref_162","first-page":"393","article-title":"Restoration of Blood-Retinal Barrier Integrity Prevents Neurodegeneration in Glaucoma","volume":"65","author":"Belforte","year":"2024","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1167\/iovs.61.3.46","article-title":"Alterations in Tight- and Adherens-Junction Proteins Related to Glaucoma Mimicked in the Organotypically Cultivated Mouse Retina Under Elevated Pressure","volume":"61","author":"Brockhaus","year":"2020","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1007\/s11033-010-0184-1","article-title":"The distribution and expression of claudin-5 and occludin at the rat blood-optic nerve barrier after borneol treatment","volume":"38","author":"Jin","year":"2011","journal-title":"Mol. Biol. Rep."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/S0092-8674(00)81553-6","article-title":"CNS myelin and sertoli cell tight junction strands are absent in Osp\/claudin-11 null mice","volume":"99","author":"Gow","year":"1999","journal-title":"Cell"},{"key":"ref_166","unstructured":"O\u2019Neal, T.B., Tripathy, K., and Luther, E.E. (2025). Retinitis Pigmentosa. StatPearls, StatPearls Publishing."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.preteyeres.2014.07.001","article-title":"Cellular responses following retinal injuries and therapeutic approaches for neurodegenerative diseases","volume":"43","author":"Cuenca","year":"2014","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_168","first-page":"175","article-title":"Histopathology of the human retina in retinitis pigmentosa","volume":"17","author":"Milam","year":"1998","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/0014-4835(92)90048-W","article-title":"Interleukin-6 (IL-6) gene expression and secretion by cytokine-stimulated human retinal pigment epithelial cells","volume":"54","author":"Elner","year":"1992","journal-title":"Exp. Eye Res."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"e126747","DOI":"10.1172\/jci.insight.126747","article-title":"Blood-retina barrier failure and vision loss in neuron-specific degeneration","volume":"5","author":"Ivanova","year":"2019","journal-title":"JCI Insight"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1055\/s-2008-1046089","article-title":"Hemodynamic findings in patients with retinitis pigmentosa","volume":"199","author":"Wolf","year":"1991","journal-title":"Klin. Monbl Augenheilkd."},{"key":"ref_172","first-page":"1487","article-title":"Association of retinal vessel attenuation with visual function in eyes with retinitis pigmentosa","volume":"8","author":"Nakagawa","year":"2014","journal-title":"Clin. Ophthalmol."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3341\/kjo.2001.15.1.1","article-title":"The effect of oxygen on retinal degeneration in wild-type and hsp70.1 knockout neonatal retinal degeneration mice","volume":"15","author":"Choi","year":"2001","journal-title":"Korean J. Ophthalmol."},{"key":"ref_174","first-page":"2427","article-title":"Photoreceptor dystrophy in the RCS rat: Roles of oxygen, debris, and bFGF","volume":"39","author":"Valter","year":"1998","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/s00417-007-0652-z","article-title":"Slowing the degenerative process, long lasting effect of hyperbaric oxygen therapy in retinitis pigmentosa","volume":"246","author":"Vingolo","year":"2008","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1083\/jcb.200201089","article-title":"Cbfa1-independent decrease in osteoblast proliferation, osteopenia, and persistent embryonic eye vascularization in mice deficient in Lrp5, a Wnt coreceptor","volume":"157","author":"Kato","year":"2002","journal-title":"J. Cell Biol."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"6452","DOI":"10.1167\/iovs.10-7146","article-title":"Frizzled 4 is required for retinal angiogenesis and maintenance of the blood-retina barrier","volume":"52","author":"Paes","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"712","DOI":"10.7150\/ijbs.45885","article-title":"Tight junctions and their regulation by non-coding RNAs","volume":"17","author":"Zhao","year":"2021","journal-title":"Int. J. Biol. Sci."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.omtn.2022.07.002","article-title":"MicroRNA-466 and microRNA-200 increase endothelial permeability in hyperglycemia by targeting Claudin-5","volume":"29","author":"Kujawa","year":"2022","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_180","doi-asserted-by":"crossref","unstructured":"Starr, C.R., and Gorbatyuk, M.S. (2023). Posttranslational modifications of proteins in diseased retina. Front. Cell. Neurosci., 17.","DOI":"10.3389\/fncel.2023.1150220"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1042\/BJ20110587","article-title":"Protein kinase Czeta phosphorylates occludin and promotes assembly of epithelial tight junctions","volume":"437","author":"Jain","year":"2011","journal-title":"Biochem. J."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"F1705","DOI":"10.1152\/ajprenal.00043.2008","article-title":"High glucose activates PKC-zeta and NADPH oxidase through autocrine TGF-beta1 signaling in mesangial cells","volume":"295","author":"Xia","year":"2008","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"2872","DOI":"10.2337\/db09-1606","article-title":"TNF-alpha signals through PKCzeta\/NF-kappaB to alter the tight junction complex and increase retinal endothelial cell permeability","volume":"59","author":"Aveleira","year":"2010","journal-title":"Diabetes"},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1146\/annurev.immunol.16.1.137","article-title":"Regulation of immune responses by TGF-beta","volume":"16","author":"Letterio","year":"1998","journal-title":"Annu. Rev. Immunol."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.ejcb.2010.10.013","article-title":"Tyrosine phosphorylation of VE-cadherin and claudin-5 is associated with TGF-beta1-induced permeability of centrally derived vascular endothelium","volume":"90","author":"Shen","year":"2011","journal-title":"Eur. J. Cell Biol."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s12987-019-0123-z","article-title":"Claudin-5: Gatekeeper of neurological function","volume":"16","author":"Greene","year":"2019","journal-title":"Fluids Barriers CNS"},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"981","DOI":"10.2337\/db19-1121","article-title":"Claudin-5 Redistribution Induced by Inflammation Leads to Anti-VEGF-Resistant Diabetic Macular Edema","volume":"69","author":"Arima","year":"2020","journal-title":"Diabetes"},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.preteyeres.2017.09.003","article-title":"Manipulating ocular endothelial tight junctions: Applications in treatment of retinal disease pathology and ocular hypertension","volume":"62","author":"Campbell","year":"2018","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"2619","DOI":"10.1093\/hmg\/dds087","article-title":"Norrin stimulates cell proliferation in the superficial retinal vascular plexus and is pivotal for the recruitment of mural cells","volume":"21","author":"Zuercher","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"ref_190","doi-asserted-by":"crossref","unstructured":"Diaz-Coranguez, M., Gonzalez-Gonzalez, L., Wang, A., Liu, X., and Antonetti, D.A. (2023). Disheveled-1 Interacts with Claudin-5 and Contributes to Norrin-Induced Endothelial Barrier Restoration. Cells, 12.","DOI":"10.3390\/cells12192402"},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.bbadis.2010.07.018","article-title":"The many faces of EMMPRIN\u2014Roles in neuroinflammation","volume":"1812","author":"Agrawal","year":"2011","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"38445","DOI":"10.1038\/srep38445","article-title":"Basigin can be a therapeutic target to restore the retinal vascular barrier function in the mouse model of diabetic retinopathy","volume":"6","author":"Arima","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.exer.2016.08.021","article-title":"Claudin-3 and claudin-19 partially restore native phenotype to ARPE-19 cells via effects on tight junctions and gene expression","volume":"151","author":"Peng","year":"2016","journal-title":"Exp. Eye Res."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1016\/S0140-6736(17)31868-8","article-title":"Efficacy and safety of voretigene neparvovec (AAV2-hRPE65v2) in patients with RPE65-mediated inherited retinal dystrophy: A randomised, controlled, open-label, phase 3 trial","volume":"390","author":"Russell","year":"2017","journal-title":"Lancet"},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"5248","DOI":"10.1111\/febs.16771","article-title":"Therapeutic applications of CRISPR\/Cas9 gene editing technology for the treatment of ocular diseases","volume":"290","author":"Sundaresan","year":"2023","journal-title":"FEBS J."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1038\/s41578-021-00358-0","article-title":"Lipid nanoparticles for mRNA delivery","volume":"6","author":"Hou","year":"2021","journal-title":"Nat. Rev. Mater."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1007\/s13346-013-0161-z","article-title":"Lipid nanoparticle delivery systems for siRNA-based therapeutics","volume":"4","author":"Wan","year":"2014","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1186\/s12967-025-07077-y","article-title":"Extracellular vesicles for targeted drug delivery: Advances in surface modification strategies and therapeutic applications","volume":"23","author":"Hu","year":"2025","journal-title":"J. Transl. Med."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1007\/s00210-022-02287-3","article-title":"Nanomedicine and drug delivery to the retina: Current status and implications for gene therapy","volume":"395","author":"Tawfik","year":"2022","journal-title":"Naunyn Schmiedebergs Arch. Pharmacol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/5\/417\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T05:23:02Z","timestamp":1772342582000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/5\/417"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,27]]},"references-count":199,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["cells15050417"],"URL":"https:\/\/doi.org\/10.3390\/cells15050417","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,27]]}}}