{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T20:23:39Z","timestamp":1790713419826,"version":"4.1.0"},"reference-count":117,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T00:00:00Z","timestamp":1780617600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"JSPS KAKENHI","award":["JP20K09824"],"award-info":[{"award-number":["JP20K09824"]}]},{"name":"JSPS KAKENHI","award":["JP25K02864"],"award-info":[{"award-number":["JP25K02864"]}]},{"award":["JP20K09824"],"award-info":[{"award-number":["JP20K09824"]}],"id":[{"id":"https:\/\/ror.org\/00hhkn466","id-type":"ROR","asserted-by":"publisher"}]},{"award":["JP25K02864"],"award-info":[{"award-number":["JP25K02864"]}],"id":[{"id":"https:\/\/ror.org\/00hhkn466","id-type":"ROR","asserted-by":"publisher"}]},{"name":"the Ministry of Health, Labour, and Welfare of Japan","award":["22FC0201"],"award-info":[{"award-number":["22FC0201"]}]},{"award":["22FC0201"],"award-info":[{"award-number":["22FC0201"]}],"id":[{"id":"https:\/\/ror.org\/03mwa7s65","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Japan Agency for Medical Research and Development, AMED","award":["23fk0108671h0001"],"award-info":[{"award-number":["23fk0108671h0001"]}]},{"name":"Japan Agency for Medical Research and Development, AMED","award":["23fk0108672h0001"],"award-info":[{"award-number":["23fk0108672h0001"]}]},{"award":["23fk0108671h0001"],"award-info":[{"award-number":["23fk0108671h0001"]}],"id":[{"id":"https:\/\/ror.org\/004rtk039","id-type":"ROR","asserted-by":"publisher"}]},{"award":["23fk0108672h0001"],"award-info":[{"award-number":["23fk0108672h0001"]}],"id":[{"id":"https:\/\/ror.org\/004rtk039","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016925","name":"the Takeda Science Foundation","doi-asserted-by":"publisher","award":["FY2023"],"award-info":[{"award-number":["FY2023"]}],"id":[{"id":"10.13039\/100016925","id-type":"DOI","asserted-by":"publisher"}]},{"award":["FY2023"],"award-info":[{"award-number":["FY2023"]}],"id":[{"id":"https:\/\/ror.org\/05xs52z55","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medical Sciences"],"abstract":"<jats:p>Uveitis is a heterogeneous group of intraocular inflammatory diseases and an important cause of visual impairment worldwide. Although current treatments mainly target inflammation, many patients develop chronic or recurrent disease, suggesting that inflammation control alone may not fully restore intraocular homeostasis. Increasing evidence highlights the blood\u2013ocular barrier (BOB), including the blood\u2013retinal barrier and blood\u2013aqueous barrier, as a key regulator of the intraocular microenvironment. This review aims to summarize the bidirectional interaction between intraocular inflammation and blood\u2013ocular barrier dysfunction in uveitis, and to highlight the clinical significance of barrier dysfunction in disease monitoring and management. In addition, this review discusses the potential value of incorporating barrier assessment into dynamic disease evaluation and relapse-aware management strategies. Recent studies suggest that inflammation and BOB dysfunction are bidirectionally linked. Inflammatory mediators disrupt barrier integrity, while barrier breakdown facilitates immune cell infiltration and further amplifies inflammation, forming a self-reinforcing cycle that may drive disease persistence. Importantly, BOB dysfunction also has clinical implications. Findings such as aqueous flare, macular edema on optical coherence tomography, and vascular leakage on fluorescein angiography reflect barrier status and can serve as dynamic indicators for disease monitoring. Persistent abnormalities despite reduced inflammatory cell activity may indicate incomplete barrier recovery or subclinical inflammation, helping to explain discordant clinical findings and the relapse-prone nature of uveitis. Rather than viewing BOB dysfunction solely as a pathological consequence of inflammation, this review highlights the potential clinical value in disease assessment and management. Barrier-related findings may provide additional information beyond conventional inflammatory evaluation, particularly in cases where inflammatory cell activity appears controlled, but underlying barrier alteration persists. Incorporating barrier assessment into monitoring may help interpret discordant clinical findings, improve evaluation of disease control, and support a more relapse-aware management strategy in uveitis. In addition, therapeutic approaches aimed at restoring barrier integrity may provide a more comprehensive strategy for achieving sustained remission and reducing recurrence risk.<\/jats:p>","DOI":"10.3390\/medsci14020290","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T08:43:04Z","timestamp":1780648984000},"page":"290","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Blood\u2013Ocular Barrier Dysfunction in Uveitis: A Bidirectional Model Linking Pathogenesis, Clinical Monitoring, and Therapeutic Opportunities"],"prefix":"10.3390","volume":"14","author":[{"given":"Yijin","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Ophthalmology and Visual Science, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Tokyo 113-8519, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingming","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Science, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Tokyo 113-8519, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1359-8198","authenticated-orcid":false,"given":"Yaru","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Science, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Tokyo 113-8519, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3124-1101","authenticated-orcid":false,"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Science, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Tokyo 113-8519, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyoko","family":"Ohno-Matsui","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Science, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Tokyo 113-8519, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koju","family":"Kamoi","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Science, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Tokyo 113-8519, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1446","DOI":"10.1038\/s41433-025-03693-6","article-title":"Comparative models of uveitis","volume":"39","author":"Knutson","year":"2025","journal-title":"Eye"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1001\/jama.2025.4358","article-title":"Uveitis in Adults: A Review","volume":"334","author":"Epps","year":"2025","journal-title":"JAMA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2104","DOI":"10.1038\/s41433-025-03854-7","article-title":"Unequal Access and Evolving Priorities in U.S. Uveitis Clinical Trials: A 23-year Analysis of Regional, Institutional, and Anatomic trends","volume":"39","author":"Shah","year":"2025","journal-title":"Eye"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"101245","DOI":"10.1016\/j.preteyeres.2024.101245","article-title":"Mechanisms of blood-retinal barrier disruption related to intraocular inflammation and malignancy","volume":"99","author":"Niederer","year":"2024","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e1479","DOI":"10.1002\/cti2.1479","article-title":"Inflammatory cytokines as mediators of retinal endothelial barrier dysfunction in non-infectious uveitis","volume":"12","author":"Ferreira","year":"2023","journal-title":"Clin. Transl. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Fan, Q., and Li, Z. (2025). Breach and restoration of retinal immune privilege: Barrier failure, innate dysregulation, and adaptive autoimmunity. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1703382"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Vinores, S.A. (2010). Breakdown of the Blood\u2013Retinal Barrier. Encycl. Eye, 216\u2013222.","DOI":"10.1016\/B978-0-12-374203-2.00137-8"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"141","DOI":"10.2147\/OPTO.S492202","article-title":"Drug-Induced Uveitis: Patterns, Pathogenesis and Clinical Implications","volume":"17","author":"Lu","year":"2025","journal-title":"Clin. Optom."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"118911","DOI":"10.1016\/j.biopha.2025.118911","article-title":"Revolutionizing uveitis treatment with nanotechnology: Innovations, barriers, and strategic solutions","volume":"194","author":"Johari","year":"2026","journal-title":"Biomed. Pharmacother."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2352019","DOI":"10.1080\/07853890.2024.2352019","article-title":"Use of corticosteroids in non-infectious uveitis\u2014Expert consensus in Taiwan","volume":"56","author":"Chang","year":"2024","journal-title":"Ann. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1016\/j.ophtha.2024.06.003","article-title":"Risk of Recurrence in Acute Anterior Uveitis","volume":"131","author":"Brodie","year":"2024","journal-title":"Ophthalmology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1016\/j.ophtha.2019.11.020","article-title":"Factors Predictive of Remission of Chronic Anterior Uveitis","volume":"127","author":"Sobrin","year":"2020","journal-title":"Ophthalmology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1080\/09273948.2023.2247077","article-title":"Psychosocial Well-Being and Quality of Life in Uveitis: A Review","volume":"32","author":"Zhang","year":"2024","journal-title":"Ocul. Immunol. Inflamm."},{"key":"ref_14","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_15","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.preteyeres.2012.10.002","article-title":"Immunological homeostasis of the eye","volume":"33","author":"Mochizuki","year":"2013","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_16","first-page":"1","article-title":"The Blood-Retinal Barrier in the Management of Retinal Disease: EURETINA Award Lecture","volume":"237","year":"2017","journal-title":"Ophthalmologica"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Wang, X., Wang, T., Lam, E., Alvarez, D., and Sun, Y. (2023). Ocular Vascular Diseases: From Retinal Immune Privilege to Inflammation. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241512090"},{"key":"ref_18","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_19","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_20","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.preteyeres.2012.10.004","article-title":"A contemporary concept of the blood-aqueous barrier","volume":"32","author":"Freddo","year":"2013","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3904","DOI":"10.1002\/jps.22610","article-title":"Comparison of drug permeabilities across the blood-retinal barrier, blood-aqueous humor barrier, and blood-brain barrier","volume":"100","author":"Toda","year":"2011","journal-title":"J. Pharm. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"S36","DOI":"10.1097\/IJG.0000000000000107","article-title":"The blood-aqueous barrier in health and disease","volume":"23","year":"2014","journal-title":"J. Glaucoma"},{"key":"ref_23","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_24","doi-asserted-by":"crossref","first-page":"100878","DOI":"10.1016\/j.preteyeres.2020.100878","article-title":"Plexus-specific retinal vascular anatomy and pathologies as seen by projection-resolved optical coherence tomographic angiography","volume":"80","author":"Hormel","year":"2021","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s13619-025-00228-y","article-title":"Preserving blood-retinal barrier integrity: A path to retinal ganglion cell protection in glaucoma and traumatic optic neuropathy","volume":"14","author":"Zhou","year":"2025","journal-title":"Cell Regen."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1097\/IAE.0b013e31826b0c41","article-title":"Proliferative vitreoretinopathy may be a risk factor in combined macular hole retinal detachment cases","volume":"33","author":"Cunningham","year":"2013","journal-title":"Retina"},{"key":"ref_27","first-page":"190724","article-title":"The retinal pigment epithelium: Something more than a constituent of the blood-retinal barrier\u2013implications for the pathogenesis of diabetic retinopathy","volume":"2010","author":"Villarroel","year":"2010","journal-title":"J. Biomed. Biotechnol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1885","DOI":"10.1038\/eye.2008.382","article-title":"Ocular immune privilege","volume":"23","author":"Taylor","year":"2009","journal-title":"Eye"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1093\/jleuko\/qiac016","article-title":"Ocular immune privilege and retinal pigment epithelial cells","volume":"113","author":"Du","year":"2023","journal-title":"J. Leukoc. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1016\/j.exer.2009.01.011","article-title":"Human iris pigment epithelium suppresses activation of bystander T cells via TGFbeta-TGFbeta receptor interaction","volume":"88","author":"Horie","year":"2009","journal-title":"Exp. Eye Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"337","DOI":"10.4103\/sjopt.sjopt_119_22","article-title":"Laser flare photometry in uveitis","volume":"36","author":"Kesim","year":"2022","journal-title":"Saudi J. Ophthalmol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"115780","DOI":"10.1016\/j.celrep.2025.115780","article-title":"Ocular immune privilege in action: The living eye imposes unique regulatory and anergic gene signatures on uveitogenic T cells","volume":"44","author":"Peng","year":"2025","journal-title":"Cell Rep."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Taylor, A.W., Hsu, S., and Ng, T.F. (2021). The Role of Retinal Pigment Epithelial Cells in Regulation of Macrophages\/Microglial Cells in Retinal Immunobiology. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.724601"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1189\/jlb.0610332","article-title":"PD-L1(hi) retinal pigment epithelium (RPE) cells elicited by inflammatory cytokines induce regulatory activity in uveitogenic T cells","volume":"88","author":"Ke","year":"2010","journal-title":"J. Leukoc. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"100950","DOI":"10.1016\/j.preteyeres.2021.100950","article-title":"Immunological aspects of RPE cell transplantation","volume":"84","author":"Sugita","year":"2021","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e23638","DOI":"10.1096\/fj.202400053R","article-title":"IL-10-induced modulation of macrophage polarization suppresses outer-blood-retinal barrier disruption in the streptozotocin-induced early diabetic retinopathy mouse model","volume":"38","author":"Lee","year":"2024","journal-title":"FASEB J."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Li, M., Yang, L., Zhai, H., Qiao, L., Wang, Z., An, X., and Wang, J. (2025). A new perspective on protecting the blood-retinal barrier against injury in diabetic retinopathy: Mitophagy. Front. Endocrinol., 16.","DOI":"10.3389\/fendo.2025.1617797"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1186\/s12974-021-02237-5","article-title":"Inflammatory resolution and vascular barrier restoration after retinal ischemia reperfusion injury","volume":"18","author":"Abcouwer","year":"2021","journal-title":"J. Neuroinflamm."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/s10456-007-9067-z","article-title":"Vascular permeability in ocular disease and the role of tight junctions","volume":"10","author":"Erickson","year":"2007","journal-title":"Angiogenesis"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Rangasamy, S., McGuire, P.G., Franco Nitta, C., Monickaraj, F., Oruganti, S.R., and Das, A. (2014). Chemokine mediated monocyte trafficking into the retina: Role of inflammation in alteration of the blood-retinal barrier in diabetic retinopathy. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0108508"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"976","DOI":"10.4103\/1673-5374.355743","article-title":"Inflammation in diabetic retinopathy: Possible roles in pathogenesis and potential implications for therapy","volume":"18","author":"Tang","year":"2023","journal-title":"Neural Regen. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"202","DOI":"10.3892\/ijmm.2025.5643","article-title":"Mechanisms of action of retinal microglia in diabetic retinopathy (Review)","volume":"56","author":"Bai","year":"2025","journal-title":"Int. J. Mol. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"781","DOI":"10.2337\/db22-0619","article-title":"Transcriptomic Profiling Reveals Chemokine CXCL1 as a Mediator for Neutrophil Recruitment Associated With Blood-Retinal Barrier Alteration in Diabetic Retinopathy","volume":"72","author":"Monickaraj","year":"2023","journal-title":"Diabetes"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/s13098-024-01282-3","article-title":"Single-cell RNA sequencing reveals roles of unique retinal microglia types in early diabetic retinopathy","volume":"16","author":"Wang","year":"2024","journal-title":"Diabetol. Metab. Syndr."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Mason, R.H., Minaker, S.A., Lahaie Luna, G., Bapat, P., Farahvash, A., Garg, A., Bhambra, N., and Muni, R.H. (2022). Changes in aqueous and vitreous inflammatory cytokine levels in proliferative diabetic retinopathy: A systematic review and meta-analysis. Eye, 1\u201351.","DOI":"10.1038\/s41433-022-02127-x"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Altmann, C., and Schmidt, M.H.H. (2018). The Role of Microglia in Diabetic Retinopathy: Inflammation, Microvasculature Defects and Neurodegeneration. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19010110"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"52","DOI":"10.4103\/0974-9233.92116","article-title":"Diabetic retinopathy and inflammation: Novel therapeutic targets","volume":"19","author":"Rangasamy","year":"2012","journal-title":"Middle East. Afr. J. Ophthalmol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"64","DOI":"10.3390\/cells10010064","article-title":"The Impact of Oxidative Stress on Blood-Retinal Barrier Physiology in Age-Related Macular Degeneration","volume":"10","author":"Tisi","year":"2021","journal-title":"Cells"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Jing, Y., and Li, D. (2025). Faricimab for retinal vein occlusion: A review of current evidence and future perspectives. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1646806"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1007\/s10792-025-03870-2","article-title":"The blood-retinal barrier in ocular pathologies: An updated narrative review","volume":"46","author":"Hang","year":"2025","journal-title":"Int. Ophthalmol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3496","DOI":"10.1167\/iovs.16-21091","article-title":"TNF\u03b1-Induced Disruption of the Blood-Retinal Barrier In Vitro Is Regulated by Intracellular 3\u2032,5\u2032-Cyclic Adenosine Monophosphate Levels","volume":"58","author":"Vogels","year":"2017","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1372","DOI":"10.1038\/s41467-024-45456-z","article-title":"Modeling early pathophysiological phenotypes of diabetic retinopathy in a human inner blood-retinal barrier-on-a-chip","volume":"15","author":"Maurissen","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1007\/s00011-021-01518-2","article-title":"PHD2 attenuates high-glucose-induced blood retinal barrier breakdown in human retinal microvascular endothelial cells by regulating the Hif-1\u03b1\/VEGF pathway","volume":"71","author":"Li","year":"2022","journal-title":"Inflamm. Res."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Zong, Y., Qiu, S., Zhang, H., Wu, J., Du, J., Kamoi, K., and Cen, Z. (2025). Antibody-based therapeutics and therapeutic development for diabetic retinopathy: Targeting VEGF, Ang\/Tie, and inflammatory pathways. Front. Endocrinol., 16.","DOI":"10.3389\/fendo.2025.1710376"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Byrne, E.M., Llori\u00e1n-Salvador, M., Tang, M., Margariti, A., Chen, M., and Xu, H. (2021). IL-17A Damages the Blood\u2013Retinal Barrier through Activating the Janus Kinase 1 Pathway. Biomedicines, 9.","DOI":"10.3390\/biomedicines9070831"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"20","DOI":"10.5115\/acb.21.227","article-title":"Blood-retina barrier dysfunction in experimental autoimmune uveitis: The pathogenesis and therapeutic targets","volume":"55","author":"Kim","year":"2022","journal-title":"Anat. Cell Biol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1167\/iovs.01-1202","article-title":"Leukocyte trafficking in experimental autoimmune uveitis: Breakdown of blood-retinal barrier and upregulation of cellular adhesion molecules","volume":"44","author":"Xu","year":"2003","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Ma, Y., Ashander, L.M., Appukuttan, B., Ryan, F.J., Tan, A.C.R., Matthews, J.M., Michael, M.Z., Lynn, D.J., and Smith, J.R. (2023). Selective Transcription Factor Blockade Reduces Human Retinal Endothelial Cell Expression of Intercellular Adhesion Molecule-1 and Leukocyte Binding. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24043304"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2872","DOI":"10.2337\/db09-1606","article-title":"TNF-\u03b1 signals through PKC\u03b6\/NF-\u03baB to alter the tight junction complex and increase retinal endothelial cell permeability","volume":"59","author":"Aveleira","year":"2010","journal-title":"Diabetes"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Sluiter, T.J., van Buul, J.D., Huveneers, S., Quax, P.H.A., and de Vries, M.R. (2021). Endothelial Barrier Function and Leukocyte Transmigration in Atherosclerosis. Biomedicines, 9.","DOI":"10.3390\/biomedicines9040328"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1007\/s00018-011-0760-0","article-title":"The biology of interleukin-1: Emerging concepts in the regulation of the actin cytoskeleton and cell junction dynamics","volume":"69","author":"Lie","year":"2012","journal-title":"Cell Mol. Life Sci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1161\/CIRCRESAHA.116.306534","article-title":"Protein Interactions at Endothelial Junctions and Signaling Mechanisms Regulating Endothelial Permeability","volume":"120","author":"Komarova","year":"2017","journal-title":"Circ. Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1167\/iovs.05-0836","article-title":"Cytokine profile in aqueous humor and sera of patients with infectious or noninfectious uveitis","volume":"47","author":"Takase","year":"2006","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e200945","DOI":"10.1172\/JCI200945","article-title":"Molecular stress and neurovascular injury in the diabetic retina","volume":"136","author":"Guo","year":"2026","journal-title":"J. Clin. Investig."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1007\/s12016-025-09038-1","article-title":"Th17 Response in Uveitis: A Double-Edged Sword in Ocular Inflammation and Immune Regulation","volume":"68","author":"Zong","year":"2025","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Fingerhut, L., Y\u00fccel, L., Strutzberg-Minder, K., von K\u00f6ckritz-Blickwede, M., Ohnesorge, B., and de Buhr, N. (2022). Ex Vivo and In Vitro Analysis Identify a Detrimental Impact of Neutrophil Extracellular Traps on Eye Structures in Equine Recurrent Uveitis. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.830871"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Bora, K., Kushwah, N., Maurya, M., Pavlovich, M.C., Wang, Z., and Chen, J. (2023). Assessment of Inner Blood\u2013Retinal Barrier: Animal Models and Methods. Cells, 12.","DOI":"10.3390\/cells12202443"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Han, J., Harper, J., Copland, D.A., and Maghsoudlou, P. (2026). The Immunopathogenesis of uveitis. Front. Med., 13.","DOI":"10.3389\/fmed.2026.1717056"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1007\/s12185-017-2293-2","article-title":"Adult T-cell leukemia cell-induced uveitis: Rapid increase in adult T-cell leukemia cells disrupts the blood\u2013ocular barrier","volume":"106","author":"Hirano","year":"2017","journal-title":"Int. J. Hematol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"20033","DOI":"10.1038\/s41598-024-68401-y","article-title":"Single-cell transcriptomic analysis of retinal immune regulation and blood-retinal barrier function during experimental autoimmune uveitis","volume":"14","author":"Quinn","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Eskandarpour, M., Nunn, M.A., Weston-Davies, W., and Calder, V.L. (2021). Immune-Mediated Retinal Vasculitis in Posterior Uveitis and Experimental Models: The Leukotriene (LT)B4-VEGF Axis. Cells, 10.","DOI":"10.3390\/cells10020396"},{"key":"ref_72","first-page":"41","article-title":"Interleukin-17A mediates Blood-Retinal Barrier breakdown in vitro and in vivo via the JAK\/STAT pathway","volume":"61","author":"Byrne","year":"2020","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1089\/jir.2011.0042","article-title":"Cytokines in autoimmune uveitis","volume":"31","author":"Horai","year":"2011","journal-title":"J. Interferon Cytokine Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"e157038","DOI":"10.1172\/jci.insight.157038","article-title":"CDCP1 regulates retinal pigmented epithelial barrier integrity for the development of experimental autoimmune uveitis","volume":"7","author":"Zhang","year":"2022","journal-title":"JCI Insight"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1006\/exer.1997.0361","article-title":"Retinal leukocyte behavior in experimental autoimmune uveoretinitis of rats","volume":"65","author":"Hamada","year":"1997","journal-title":"Exp. Eye Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.exer.2015.06.017","article-title":"ICAM-1 and VCAM-1 are differentially expressed on blood-retinal barrier cells during experimental autoimmune uveitis","volume":"137","author":"Dewispelaere","year":"2015","journal-title":"Exp. Eye Res."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Mirando, A.C., Lima, E.S.R., Chu, Z., Campochiaro, P.A., Pandey, N.B., and Popel, A.S. (2020). Suppression of Ocular Vascular Inflammation through Peptide-Mediated Activation of Angiopoietin-Tie2 Signaling. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21145142"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2337","DOI":"10.1111\/febs.16177","article-title":"Myeloid cells in retinal and brain degeneration","volume":"289","author":"Guo","year":"2022","journal-title":"FEBS J."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s40662-021-00239-1","article-title":"Neurovascular unit in diabetic retinopathy: Pathophysiological roles and potential therapeutical targets","volume":"8","author":"Nian","year":"2021","journal-title":"Eye Vis."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Tan, T.E., and Wong, T.Y. (2022). Diabetic retinopathy: Looking forward to 2030. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.1077669"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Stofkova, A., Zloh, M., Andreanska, D., Fiserova, I., Kubovciak, J., Hejda, J., Kutilek, P., and Murakami, M. (2021). Depletion of Retinal Dopaminergic Activity in a Mouse Model of Rod Dysfunction Exacerbates Experimental Autoimmune Uveoretinitis: A Role for the Gateway Reflex. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23010453"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s42234-019-0030-2","article-title":"Neural activity regulates autoimmune diseases through the gateway reflex","volume":"5","author":"Stofkova","year":"2019","journal-title":"Bioelectron. Med."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.ajo.2018.02.019","article-title":"Autoimmunity, Autoinflammation, and Infection in Uveitis","volume":"189","author":"Forrester","year":"2018","journal-title":"Am. J. Ophthalmol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"3073","DOI":"10.1172\/JCI42440","article-title":"A look at autoimmunity and inflammation in the eye","volume":"120","author":"Caspi","year":"2010","journal-title":"J. Clin. Investig."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1007\/s10792-016-0253-0","article-title":"The importance of quantitative measurement methods for uveitis: Laser flare photometry endorsed in Europe while neglected in Japan where the technology measuring quantitatively intraocular inflammation was developed","volume":"37","author":"Herbort","year":"2017","journal-title":"Int. Ophthalmol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1159\/000027306","article-title":"Correlation between anterior chamber IgG\/albumin concentrations and laser flare photometry in eyes with endogenous uveitis","volume":"212","author":"Chiou","year":"1998","journal-title":"Ophthalmologica"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.ajo.2025.06.029","article-title":"Evidence and Consensus-based Imaging Guidelines in Birdshot Chorioretinopathy: Multimodal Imaging in Uveitis (MUV) Taskforce Report 8","volume":"278","author":"Pichi","year":"2025","journal-title":"Am. J. Ophthalmol."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Sota, J., Mej\u00eda-Salgado, G., Guerriero, S., Ragab, G., Costi, S., Paroli, M.P., Hinojosa-Azaola, A., Lopalco, G., Breda, L., and Giardini, H.A.M. (2025). Predictors of uveitic macular edema and functional prognostic outcomes: Real-life data from the international AIDA Network uveitis registry. Front. Med., 12.","DOI":"10.3389\/fmed.2025.1609613"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1080\/09273948.2019.1709650","article-title":"Non-invasive Instrument-Based Tests for Quantifying Anterior Chamber Flare in Uveitis: A Systematic Review","volume":"29","author":"Liu","year":"2021","journal-title":"Ocul. Immunol. Inflamm."},{"key":"ref_90","first-page":"662","article-title":"The Value of Laser Flare Photometry as a Monitoring Tool for Uveitis","volume":"240","author":"Tappeiner","year":"2022","journal-title":"Klin. Monatsbl. Augenheilkd."},{"key":"ref_91","first-page":"1653","article-title":"Characteristic analysis of fundus fluorescein angiography and optical coherence tomography findings in uveitis","volume":"37","author":"Chen","year":"2017","journal-title":"J. Shanghai Jiaotong Univ. (Med. Sci.)"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.survophthal.2004.10.004","article-title":"Laser flare-cell photometry: Methodology and clinical applications","volume":"50","author":"Ladas","year":"2005","journal-title":"Surv. Ophthalmol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1038\/eye.2016.133","article-title":"Spectral-domain optical coherence tomography findings of the macula in 500 consecutive patients with uveitis","volume":"30","author":"Grajewski","year":"2016","journal-title":"Eye"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1016\/j.oret.2017.01.016","article-title":"Peripheral Findings and Retinal Vascular Leakage on Ultra-Widefield Fluorescein Angiography in Patients with Uveitis","volume":"1","author":"Pecen","year":"2017","journal-title":"Ophthalmol. Retin."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s12348-019-0193-8","article-title":"Automated measurement of leakage on wide-field angiography in the assessment of retinal vasculitis","volume":"10","author":"Venkat","year":"2020","journal-title":"J. Ophthalmic Inflamm. Infect."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"8612","DOI":"10.1038\/s41598-019-45149-4","article-title":"Association between subfoveal choroidal thickness and leakage site on fluorescein angiography in Beh\u00e7et\u2019s uveitis","volume":"9","author":"Shirahama","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1007\/s00417-008-0823-6","article-title":"Use of laser flare-cell photometry to quantify intraocular inflammation in patients with Beh\u00e7et uveitis","volume":"246","author":"Kir","year":"2008","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"41","DOI":"10.3109\/09273948.2015.1108444","article-title":"Evaluation of Intraocular Inflammation with Laser Flare Photometry in Beh\u00e7et Uveitis","volume":"25","author":"Yalcindag","year":"2017","journal-title":"Ocul. Immunol. Inflamm."},{"key":"ref_99","unstructured":"Sood, G., and Patel, B.C. (2023). Uveitic Macular Edema. StatPearls, StatPearls Publishing."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1080\/09273948.2019.1576910","article-title":"Epidemiology of Macular Edema in Uveitis","volume":"27","author":"Accorinti","year":"2019","journal-title":"Ocul. Immunol. Inflamm."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Haydinger, C.D., Ferreira, L.B., Williams, K.A., and Smith, J.R. (2023). Mechanisms of macular edema. Front. Med., 10.","DOI":"10.3389\/fmed.2023.1128811"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"14","DOI":"10.2478\/v10153-011-0092-8","article-title":"Macular edema in uveitis","volume":"54","year":"2012","journal-title":"Folia Med."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2893","DOI":"10.1007\/s00417-025-06899-2","article-title":"Burden of macular complications in Japanese patients aged 75 years and over with sarcoid uveitis","volume":"263","author":"Zong","year":"2025","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Tungsattayathitthan, U., Jenjanya, S., Choopong, P., Sanphan, W., Tesavibul, N., and Boonsopon, S. (2024). Prevalence, clinical characteristics, and independent predictors of uveitic macular edema in an Asian population: A retrospective cohort study. BMC Ophthalmol., 24.","DOI":"10.1186\/s12886-024-03447-0"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"101000","DOI":"10.1016\/j.xops.2025.101000","article-title":"Detecting Inflammation in Fundus Photographs Using Machine Learning","volume":"6","author":"Mohammadi","year":"2026","journal-title":"Ophthalmol. Sci."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1007\/978-3-031-72230-1_2","article-title":"Fluorescein Angiography","volume":"1467","author":"Andrade","year":"2025","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Kang, H., Wu, X., Xu, H., Huang, Y., and Zhang, M. (2025). Effectiveness and safety of tocilizumab in refractory noninfectious uveitis: A systematic review and meta-analysis. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1694311"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"22227","DOI":"10.1038\/s41598-020-78718-z","article-title":"A 10-year follow-up of infliximab monotherapy for refractory uveitis in Beh\u00e7et\u2019s syndrome","volume":"10","author":"Horiguchi","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1080\/09273948.2018.1491605","article-title":"Adalimumab in Active and Inactive, Non-Infectious Uveitis: Global Results from the VISUAL I and VISUAL II Trials","volume":"27","author":"Goto","year":"2019","journal-title":"Ocul. Immunol. Inflamm."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"112460","DOI":"10.1016\/j.intimp.2024.112460","article-title":"Evaluating tocilizumab safety and immunomodulatory effects under ocular HTLV-1 infection in vitro","volume":"137","author":"Zhang","year":"2024","journal-title":"Int. Immunopharmacol."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Zong, Y., Miyagaki, M., Yang, M., Zhang, J., Zou, Y., Ohno-Matsui, K., and Kamoi, K. (2024). Ophthalmic Use of Targeted Biologics in the Management of Intraocular Diseases: Current and Emerging Therapies. Antibodies, 13.","DOI":"10.3390\/antib13040086"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.ajo.2020.04.043","article-title":"Epidemiology and Clinical Characteristics of Episcleritis and Scleritis in Olmsted County, Minnesota","volume":"217","author":"Xu","year":"2020","journal-title":"Am. J. Ophthalmol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1852","DOI":"10.4103\/ijo.IJO_1548_20","article-title":"Systemic immunosuppressive therapies for uveitis in developing countries","volume":"68","author":"Agrawal","year":"2020","journal-title":"Indian J. Ophthalmol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1056\/NEJMoa1509852","article-title":"Adalimumab in Patients with Active Noninfectious Uveitis","volume":"375","author":"Jaffe","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"13117","DOI":"10.2147\/JIR.S533011","article-title":"Tocilizumab for Non-Infectious Uveitis: A Systematic Review","volume":"18","author":"Cao","year":"2025","journal-title":"J. Inflamm. Res."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1007\/s10238-022-00954-6","article-title":"Pathogenesis and current therapies for non-infectious uveitis","volume":"23","author":"Wu","year":"2023","journal-title":"Clin. Exp. Med."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1007\/s10384-025-01310-3","article-title":"Recent advances in the diagnosis and treatment of refractory ocular inflammatory diseases: Focus on uveitic macular edema, acute retinal necrosis, and vitreoretinal lymphoma","volume":"70","author":"Takeda","year":"2025","journal-title":"Jpn. J. Ophthalmol."}],"container-title":["Medical Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3271\/14\/2\/290\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T09:27:41Z","timestamp":1780651661000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3271\/14\/2\/290"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,5]]},"references-count":117,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["medsci14020290"],"URL":"https:\/\/doi.org\/10.3390\/medsci14020290","relation":{},"ISSN":["2076-3271"],"issn-type":[{"value":"2076-3271","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,5]]}}}