{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T11:31:51Z","timestamp":1768476711922,"version":"3.49.0"},"reference-count":62,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2011,11,23]],"date-time":"2011-11-23T00:00:00Z","timestamp":1322006400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Nanoparticles are nanometer-scaled particles, and can be utilized in the form of nanocapsules, nanoconjugates, or nanoparticles themselves for the treatment of retinopathy, including angiogensis-related blindness, retinal degeneration, and uveitis. They are thought to improve the bioavailability in the retina and the permeability of therapeutic molecules across the barriers of the eye, such as the cornea, conjunctiva, and especially, blood-retinal barriers (BRBs). However, consisting of multiple neuronal cells, the retina can be the target of neuronal toxicity of nanoparticles, in common with the central and peripheral nervous system. Furthermore, the ability of nanoparticles to pass through the BRBs might increase the possibility of toxicity, simultaneously promoting distribution in the retinal layers. In this regard, we discussed nanotechnology and nanotoxicology in the treatment of retinopathy.<\/jats:p>","DOI":"10.3390\/ijms12118288","type":"journal-article","created":{"date-parts":[[2011,11,23]],"date-time":"2011-11-23T11:12:28Z","timestamp":1322046748000},"page":"8288-8301","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Nanotechnology and Nanotoxicology in Retinopathy"],"prefix":"10.3390","volume":"12","author":[{"given":"Dong Hyun","family":"Jo","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, College of Medicine, Seoul National University, Seoul 110-744, Korea"},{"name":"Fight against Angiogenesis-Related Blindness (FARB) Laboratory, Clinical Research Institute, Seoul National University Hospital, Seoul 110-744, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tae Geol","family":"Lee","sequence":"additional","affiliation":[{"name":"Center for Nano-Bio Technology, Division of Convergence Technology, Korea Research Institute of Standards and Science (KRISS), Daejon 305-340, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeong Hun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, College of Medicine, Seoul National University, Seoul 110-744, Korea"},{"name":"Fight against Angiogenesis-Related Blindness (FARB) Laboratory, Clinical Research Institute, Seoul National University Hospital, Seoul 110-744, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2011,11,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/2040-2384-2-21","article-title":"The potential of nanomedicine therapies to treat neovascular disease in the retina","volume":"2","author":"Farjo","year":"2010","journal-title":"J. Angiogenes. Res"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1016\/j.preteyeres.2010.08.002","article-title":"Applications of nanoparticles in ophthalmology","volume":"29","author":"Diebold","year":"2010","journal-title":"Prog. Retin. Eye Res"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.drudis.2010.12.004","article-title":"Drug delivery to the posterior segment of the eye","volume":"16","author":"Thrimawithana","year":"2011","journal-title":"Drug Discov. Today"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1007\/s12272-010-1007-6","article-title":"How to overcome retinal neuropathy: The fight against angiogenesis-related blindness","volume":"33","author":"Jo","year":"2010","journal-title":"Arch. Pharm. Res"},{"key":"ref_5","first-page":"339","article-title":"Blood-neural barrier: Intercellular communication at glio-vascular interface","volume":"39","author":"Kim","year":"2006","journal-title":"J. Biochem. Mol. Biol"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1007\/BF00146764","article-title":"The blood-retinal barriers","volume":"41","year":"1976","journal-title":"Doc. Ophthalmol"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"505101","DOI":"10.1088\/0957-4484\/20\/50\/505101","article-title":"Intravenously administered gold nanoparticles pass through the blood-retinal barrier depending on the particle size, and induce no retinal toxicity","volume":"20","author":"Kim","year":"2009","journal-title":"Nanotechnology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.1016\/j.biomaterials.2010.11.030","article-title":"The inhibition of retinal neovascularization by gold nanoparticles via suppression of vegfr-2 activation","volume":"32","author":"Kim","year":"2011","journal-title":"Biomaterials"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/s10456-010-9193-x","article-title":"Gold nanoparticles inhibit vascular endothelial growth factor-induced angiogenesis and vascular permeability via src dependent pathway in retinal endothelial cells","volume":"14","author":"Kalishwaralal","year":"2011","journal-title":"Angiogenesis"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e16733","DOI":"10.1371\/journal.pone.0016733","article-title":"Nanoceria inhibit the development and promote the regression of pathologic retinal neovascularization in the vldlr knockout mouse","volume":"6","author":"Zhou","year":"2011","journal-title":"PLoS One"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.jconrel.2009.10.031","article-title":"Nanoparticle-integrin antagonist c16y peptide treatment of choroidal neovascularization in rats","volume":"142","author":"Kim","year":"2010","journal-title":"J. Control. Release"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1038\/gt.2008.185","article-title":"Intravenous transferrin, rgd peptide and dual-targeted nanoparticles enhance anti-vegf intraceptor gene delivery to laser-induced cnv","volume":"16","author":"Singh","year":"2009","journal-title":"Gene Ther"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"6230","DOI":"10.1167\/iovs.10-6229","article-title":"Anti-inflammatory and antiangiogenic effects of nanoparticle-mediated delivery of a natural angiogenic inhibitor","volume":"52","author":"Jin","year":"2011","journal-title":"Invest. Ophthalmol. Vis. Sci"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1902","DOI":"10.2337\/db08-1327","article-title":"Nanoparticle-mediated expression of an angiogenic inhibitor ameliorates ischemia-induced retinal neovascularization and diabetes-induced retinal vascular leakage","volume":"58","author":"Park","year":"2009","journal-title":"Diabetes"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Jo, D.H., Kim, J.H., Yu, Y.S., Lee, T.G., and Kim, J.H. (2011). Antiangiogenic effect of silicate nanoparticle on retinal neovascularization induced by vascular endothelial growth factor. Nanomedicine, In press.","DOI":"10.1016\/j.nano.2011.09.003"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.colsurfb.2009.04.025","article-title":"Silver nanoparticles inhibit vegf induced cell proliferation and migration in bovine retinal endothelial cells","volume":"73","author":"Kalishwaralal","year":"2009","journal-title":"Colloids Surf. B"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.jconrel.2010.03.022","article-title":"Silver nano - a trove for retinal therapies","volume":"145","author":"Kalishwaralal","year":"2010","journal-title":"J. Control Release"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3381","DOI":"10.1167\/iovs.06-1242","article-title":"Prolonged protective effect of basic fibroblast growth factor-impregnated nanoparticles in royal college of surgeons rats","volume":"48","author":"Sakai","year":"2007","journal-title":"Invest. Ophthalmol. Vis. Sci"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"18706","DOI":"10.1073\/pnas.1007644107","article-title":"Inhibition of ceramide biosynthesis preserves photoreceptor structure and function in a mouse model of retinitis pigmentosa","volume":"107","author":"Strettoi","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1038\/nnano.2006.91","article-title":"Rare earth nanoparticles prevent retinal degeneration induced by intracellular peroxides","volume":"1","author":"Chen","year":"2006","journal-title":"Nat. Nanotechnol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1016\/j.nbd.2011.03.004","article-title":"Nanoceria extend photoreceptor cell lifespan in tubby mice by modulation of apoptosis\/survival signaling pathways","volume":"42","author":"Kong","year":"2011","journal-title":"Neurobiol. Dis"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1038\/mt.2010.167","article-title":"Pod nanoparticles expressing gdnf provide structural and functional rescue of light-induced retinal degeneration in an adult mouse","volume":"18","author":"Read","year":"2010","journal-title":"Mol. Ther"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1096\/fj.09-139147","article-title":"Gene delivery to mitotic and postmitotic photoreceptors via compacted DNA nanoparticles results in improved phenotype in a mouse model of retinitis pigmentosa","volume":"24","author":"Cai","year":"2010","journal-title":"FASEB J"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e5290","DOI":"10.1371\/journal.pone.0005290","article-title":"A partial structural and functional rescue of a retinitis pigmentosa model with compacted DNA nanoparticles","volume":"4","author":"Cai","year":"2009","journal-title":"PLoS One"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3702","DOI":"10.1002\/eji.200425022","article-title":"Intraocular injection of tamoxifen-loaded nanoparticles: A new treatment of experimental autoimmune uveoretinitis","volume":"34","author":"Andrieux","year":"2004","journal-title":"Eur. J. Immunol"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1016\/j.exer.2005.09.003","article-title":"Treatment of experimental autoimmune uveoretinitis with poly(lactic acid) nanoparticles encapsulating betamethasone phosphate","volume":"82","author":"Sakai","year":"2006","journal-title":"Exp. Eye Res"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e3554","DOI":"10.1371\/journal.pone.0003554","article-title":"Endogenous vegf is required for visual function: Evidence for a survival role on muller cells and photoreceptors","volume":"3","author":"Maharaj","year":"2008","journal-title":"PLoS One"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1089\/jop.2008.0092","article-title":"Enlargement of the foveal avascular zone in diabetic retinopathy after adjunctive intravitreal bevacizumab (avastin) with pars plana vitrectomy","volume":"25","author":"Lee","year":"2009","journal-title":"J. Ocul. Pharmacol. Ther"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.1167\/iovs.06-0828","article-title":"Preclinical safety evaluation of intravitreal injection of full-length humanized vascular endothelial growth factor antibody in rabbit eyes","volume":"48","author":"Inan","year":"2007","journal-title":"Invest. Ophthalmol. Vis. Sci"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3530","DOI":"10.1158\/1078-0432.CCR-04-2482","article-title":"Antiangiogenic properties of gold nanoparticles","volume":"11","author":"Mukherjee","year":"2005","journal-title":"Clin. Cancer Res"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/S0168-3659(03)00328-6","article-title":"Polymer degradation and in vitro release of a model protein from poly(d,l-lactide-co-glycolide) nano- and microparticles","volume":"92","author":"Panyam","year":"2003","journal-title":"J. Control. Release"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/S0169-409X(02)00228-4","article-title":"Biodegradable nanoparticles for drug and gene delivery to cells and tissue","volume":"55","author":"Panyam","year":"2003","journal-title":"Adv. Drug Deliv. Rev"},{"key":"ref_33","first-page":"1295","article-title":"Animal models and different therapies for treatment of retinitis pigmentosa","volume":"24","author":"Rivas","year":"2009","journal-title":"Histol. Histopathol"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"183","DOI":"10.3109\/13816810.2010.499887","article-title":"Historical evolution in the understanding of stargardt macular dystrophy","volume":"31","author":"Fishman","year":"2010","journal-title":"Ophthalmic. Genet"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1136\/bjo.2009.174912","article-title":"Gene therapy for ocular diseases","volume":"95","author":"Liu","year":"2011","journal-title":"Br. J. Ophthalmol"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1517\/14656561003713534","article-title":"Pharmacotherapy of uveitis","volume":"11","author":"Lee","year":"2010","journal-title":"Expert Opin. Pharmacother"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1167\/iovs.02-0375","article-title":"Biodegradable intrascleral implant for sustained intraocular delivery of betamethasone phosphate","volume":"44","author":"Okabe","year":"2003","journal-title":"Invest. Ophthalmol. Vis. Sci"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1916","DOI":"10.1016\/j.ophtha.2011.07.027","article-title":"Randomized comparison of systemic anti-inflammatory therapy versus fluocinolone acetonide implant for intermediate, posterior, and panuveitis: The multicenter uveitis steroid treatment trial","volume":"118","author":"Kempen","year":"2011","journal-title":"Ophthalmology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3307","DOI":"10.1016\/j.visres.2004.07.041","article-title":"Visual experience and maturation of retinal synaptic pathways","volume":"44","author":"Tian","year":"2004","journal-title":"Vision Res"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3562","DOI":"10.1167\/iovs.02-1068","article-title":"Ocular drug delivery targeting the retina and retinal pigment epithelium using polylactide nanoparticles","volume":"44","author":"Bourges","year":"2003","journal-title":"Invest. Ophthalmol. Vis. Sci"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1587","DOI":"10.1016\/S0142-9612(01)00284-8","article-title":"Ocular disposition and tolerance of ganciclovir-loaded albumin nanoparticles after intravitreal injection in rats","volume":"23","author":"Merodio","year":"2002","journal-title":"Biomaterials"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1097\/IAE.0b013e3180dc9360","article-title":"Absence of histologic retinal toxicity of intravitreal nanogold in a rabbit model","volume":"28","author":"Bakri","year":"2008","journal-title":"Retina"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e7410","DOI":"10.1371\/journal.pone.0007410","article-title":"Ocular delivery of compacted DNA-nanoparticles does not elicit toxicity in the mouse retina","volume":"4","author":"Ding","year":"2009","journal-title":"PLoS One"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1021\/mp900083m","article-title":"Cell uptake and in vitro toxicity of magnetic nanoparticles suitable for drug delivery","volume":"6","author":"Hafeli","year":"2009","journal-title":"Mol. Pharm"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.nano.2008.06.003","article-title":"Ocular nanoparticle toxicity and transfection of the retina and retinal pigment epithelium","volume":"4","author":"Prow","year":"2008","journal-title":"Nanomedicine"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1289\/ehp.0901661","article-title":"Nanoparticles induce changes of the electrical activity of neuronal networks on microelectrode array neurochips","volume":"118","author":"Gramowski","year":"2010","journal-title":"Environ. Health Perspect"},{"key":"ref_47","first-page":"481","article-title":"Toxicological effects of titanium dioxide nanoparticles: A review of in vitro mammalian studies","volume":"15","author":"Iavicoli","year":"2011","journal-title":"Eur. Rev. Med. Pharmacol. Sci"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.toxlet.2009.01.020","article-title":"Expression of genes related to oxidative stress in the mouse brain after exposure to silver-25 nanoparticles","volume":"187","author":"Rahman","year":"2009","journal-title":"Toxicol. Lett"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1016\/j.neuro.2009.09.005","article-title":"Expression changes of dopaminergic system-related genes in pc12 cells induced by manganese, silver, or copper nanoparticles","volume":"30","author":"Wang","year":"2009","journal-title":"Neurotoxicology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1289\/ehp.0901534","article-title":"Silica-based nanoparticle uptake and cellular response by primary microglia","volume":"118","author":"Choi","year":"2010","journal-title":"Environ. Health Perspect"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2595","DOI":"10.1021\/nn901869f","article-title":"Microglial response to gold nanoparticles","volume":"4","author":"Hutter","year":"2010","journal-title":"ACS Nano"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1002\/smll.201002287","article-title":"Interaction of spherical silica nanoparticles with neuronal cells: Size-dependent toxicity and perturbation of calcium homeostasis","volume":"7","author":"Ariano","year":"2011","journal-title":"Small"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.tox.2009.08.005","article-title":"Action potential changes associated with the inhibitory effects on voltage-gated sodium current of hippocampal ca1 neurons by silver nanoparticles","volume":"264","author":"Liu","year":"2009","journal-title":"Toxicology"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"150","DOI":"10.3109\/17435390903337693","article-title":"Copper nanoparticles exert size and concentration dependent toxicity on somatosensory neurons of rat","volume":"4","author":"Prabhu","year":"2010","journal-title":"Nanotoxicology"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1002\/anie.201001037","article-title":"Nanotoxicology: An interdisciplinary challenge","volume":"50","author":"Krug","year":"2011","journal-title":"Angew. Chem. Int. Ed. Engl"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1912","DOI":"10.1016\/j.biomaterials.2007.12.037","article-title":"Particle size-dependent organ distribution of gold nanoparticles after intravenous administration","volume":"29","author":"Hagens","year":"2008","journal-title":"Biomaterials"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"115101","DOI":"10.1088\/0957-4484\/20\/11\/115101","article-title":"Nanosized zinc oxide particles induce neural stem cell apoptosis","volume":"20","author":"Deng","year":"2009","journal-title":"Nanotechnology"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/j.bbrc.2010.02.046","article-title":"Bioaccumulation and toxicity of gold nanoparticles after repeated administration in mice","volume":"393","author":"Barria","year":"2010","journal-title":"Biochem. Biophys. Res. Commun"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.tox.2008.09.014","article-title":"Time-dependent translocation and potential impairment on central nervous system by intranasally instilled tio(2) nanoparticles","volume":"254","author":"Wang","year":"2008","journal-title":"Toxicology"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1021\/bc049951i","article-title":"Toxicity of gold nanoparticles functionalized with cationic and anionic side chains","volume":"15","author":"Goodman","year":"2004","journal-title":"Bioconjug. Chem"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1080\/10611860400015936","article-title":"Nanoparticle surface charges alter blood-brain barrier integrity and permeability","volume":"12","author":"Lockman","year":"2004","journal-title":"J. Drug Target"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"532","DOI":"10.3109\/08958378.2011.592869","article-title":"Amorphous silica coatings on magnetic nanoparticles enhance stability and reduce toxicity to in vitro beas-2b cells","volume":"23","author":"Baber","year":"2011","journal-title":"Inhal. Toxicol"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/12\/11\/8288\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:58:07Z","timestamp":1760219887000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/12\/11\/8288"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,11,23]]},"references-count":62,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2011,11]]}},"alternative-id":["ijms12118288"],"URL":"https:\/\/doi.org\/10.3390\/ijms12118288","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,11,23]]}}}