Dual Role of Intravitreous Infliximab in Experimental Choroidal Neovascularization: Effect on the Expression of Sulfated Glycosaminoglycans

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dc.contributor.author Regatieri, Caio Vinicius Saito [UNIFESP]
dc.contributor.author Dreyfuss, Juliana Luporini [UNIFESP]
dc.contributor.author Melo, Gustavo Barreto de [UNIFESP]
dc.contributor.author Lavinsky, Daniel [UNIFESP]
dc.contributor.author Farah, Michel Eid [UNIFESP]
dc.contributor.author Nader, Helena Bonciani [UNIFESP]
dc.date.accessioned 2016-01-24T13:58:51Z
dc.date.available 2016-01-24T13:58:51Z
dc.date.issued 2009-11-01
dc.identifier http://dx.doi.org/10.1167/iovs.08-3171
dc.identifier.citation Investigative Ophthalmology & Visual Science. Rockville: Assoc Research Vision Ophthalmology Inc, v. 50, n. 11, p. 5487-5494, 2009.
dc.identifier.issn 0146-0404
dc.identifier.uri http://repositorio.unifesp.br/handle/11600/31906
dc.description.abstract PURPOSE. To determine effects of intravitreous anti-TNF-alpha (infliximab) in a laser-induced choroidal neovascularization (CNV) model by fluorescein angiogram (FA), immunofluorescence, ELISA, and glycosaminoglycan analyses.METHODS. CNV induction was performed using argon laser. Rats were divided into eight groups (no-laser no-infliximab; laser; laser with 10, 20, 40, 80, or 320 mu g infliximab; and isotype-matched IgG). After 3 weeks, CNV area was measured by FA and von Willebrand factor (vWF) immunofluorescence. VEGF, TGF-beta, and syndecan-4 were evaluated by ELISA and immunofluorescence. Glycosaminoglycan expression was determined in retina and choroid of animals metabolically labeled with [(35)S]-sulfate. Cytotoxicity was investigated using ARPE-19 and endothelial cells.RESULTS. FA showed significant reduction in the low-dose infliximab groups (10-40 mu g), confirmed by vWF immunofluorescence that showed 49% decrease in the CNV. VEGF and TGF-beta decreased expression detected by ELISA and immunofluorescence paralleled these results. Similar data were observed for syndecan-4. the expression of these molecules in the neovascularization area using 320 mu g was similar to the no-infliximab laser group or laser with isotype-matched IgG. Heparan sulfate expression in retina and choroid paralleled the observed effects on angiogenesis. Increased expression of chondroitin sulfate in retina and dermatan sulfate in choroid reflects the effects of injury and fibrosis using high doses of anti-TNF-alpha. Infliximab showed no cytotoxic effect in ARPE-19 cells, whereas high doses led to 20% decrease in endothelial cell viability.CONCLUSIONS. Intravitreal infliximab shows dual effect on the development of laser-induced CNV. It reduces angiogenesis and glycosaminoglycan expression at low doses, whereas opposite effects are observed at high doses. (Invest Ophthalmol Vis Sci. 2009;50:5487-5494) DOI: 10.1167/iovs.08-3171 en
dc.description.sponsorship Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorship Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorship Vision Institute from UNIFESP Ophthalmology Department
dc.description.sponsorship Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorship FapUnifesp
dc.format.extent 5487-5494
dc.language.iso eng
dc.publisher Assoc Research Vision Ophthalmology Inc
dc.relation.ispartof Investigative Ophthalmology & Visual Science
dc.rights Acesso aberto
dc.title Dual Role of Intravitreous Infliximab in Experimental Choroidal Neovascularization: Effect on the Expression of Sulfated Glycosaminoglycans en
dc.type Artigo
dc.contributor.institution Universidade Federal de São Paulo (UNIFESP)
dc.description.affiliation Universidade Federal de São Paulo, Div Mol Biol, Dept Biochem, São Paulo, Brazil
dc.description.affiliation Universidade Federal de São Paulo, Dept Ophthalmol, São Paulo, Brazil
dc.description.affiliationUnifesp Universidade Federal de São Paulo, Div Mol Biol, Dept Biochem, São Paulo, Brazil
dc.description.affiliationUnifesp Universidade Federal de São Paulo, Dept Ophthalmol, São Paulo, Brazil
dc.identifier.doi 10.1167/iovs.08-3171
dc.description.source Web of Science
dc.identifier.wos WOS:000271429200062



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