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Título: | Protective Effect of a GLP-1 Analog on Ischemia-Reperfusion Induced Blood-Retinal Barrier Breakdown and Inflammation | Autor: | Gonçalves, Andreia Lin, Cheng-Mao Muthusamy, Arivalagan Fontes-Ribeiro, Carlos A. Ambrósio, António F. Abcouwer, Steven F Fernandes, Rosa Antonetti, David A. |
Palavras-chave: | blood–brain barrier; inflammation; ischemia-reperfusion injury; microglia; vascular biology | Data: | 1-Mai-2016 | Editora: | Association for Research in Vision and Ophthalmology | Projeto: | Supported by NIH R01 EY012021 (DAA); Research to Prevent Blindness Jules and Doris Stein Professorship (DAA); NIH R01 EY007739 (SFA); the Core Center for Vision Research at the Kellogg Eye Center P30 EY007003; European Foundation for the Study of Diabetes (EFSD)/Glaxo Smith Kline Programme (RF); GIFT/Portuguese Society of Diabetes (RF); Foundation for Science and Technology (FCT Portugal, Strategic Project UID/NEU/04539/ 2013, Project PTDC/NEU-OSD/1113/2012-FCOMP-0124-FEDER- 029665 (AFA); PhD fellowship SFRH/BD/103936/2014 (AG); COMPETE-FEDER; and a Fulbright Research Fellowship (AG). | Título da revista, periódico, livro ou evento: | Investigative Ophthalmology and Visual Science | Volume: | 57 | Número: | 6 | Resumo: | PURPOSE. Inflammation associated with blood–retinal barrier (BRB) breakdown is a common feature of several retinal diseases. Therefore, the development of novel nonsteroidal antiinflammatory approaches may provide important therapeutic options. Previous studies demonstrated that inhibition of dipeptidyl peptidase-IV, the enzyme responsible for the degradation of glucagon-like peptide-1 (GLP-1), led to insulin-independent prevention of diabetes-induced increases in BRB permeability, suggesting that incretin-based drugs may have beneficial pleiotropic effects in the retina. In the current study, the barrier protective and antiinflammatory properties of exendin-4 (Ex-4), an analog of GLP-1, after ischemia-reperfusion (IR) injury were examined. METHODS. Ischemia-reperfusion injury was induced in rat retinas by increasing the intraocular pressure for 45 minutes followed by 48 hours of reperfusion. Rats were treated with Ex-4 prior to and following IR. Blood–retinal barrier permeability was assessed by Evans blue dye leakage. Retinal inflammatory gene expression and leukocytic infiltration were measured by qRT-PCR and immunofluorescence, respectively. A microglial cell line was used to determine the effects of Ex-4 on lipopolysaccharide (LPS)-induced inflammatory response. RESULTS. Exendin-4 dramatically reduced the BRB permeability induced by IR injury, which was associated with suppression of inflammatory gene expression. Moreover, in vitro studies showed that Ex-4 also reduced the inflammatory response to LPS and inhibited NF-jB activation. CONCLUSIONS. The present work suggests that Ex-4 can prevent IR injury–induced BRB breakdown and inflammation through inhibition of inflammatory cytokine production by activated microglia and may provide a novel option for therapeutic intervention in diseases involving retinal inflammation. | URI: | https://hdl.handle.net/10316/108638 | ISSN: | 1552-5783 | DOI: | 10.1167/iovs.15-19006 | Direitos: | openAccess |
Aparece nas coleções: | FMUC Medicina - Artigos em Revistas Internacionais |
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Protective effect of a GLP-1 analog on ischemia-reperfusion induced blood–retinal barrier breakdown and inflammation.pdf | 1.28 MB | Adobe PDF | Ver/Abrir |
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