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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/159017
Topical administration of bosentan prevents retinal neurodegeneration in experimental diabetes
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Experimental evidence suggests that endothelin 1 (ET-1) is involved in the development of retinal microvascular abnormalities induced by diabetes. The effects of ET-1 are mediated by endothelin A- and B-receptors (ETA and ETB). Endothelin B-receptors activation mediates retinal neurodegeneration but there are no data regarding the effectiveness of ETB receptor blockage in arresting retinal neurodegeneration induced by diabetes. The main aim of the present study was to assess the usefulness of topical administration of bosentan (a dual endothelin receptor antagonist) in preventing retinal neurodegeneration in diabetic (db/db) mice. For this purpose, db/db mice aged 10 weeks were treated with one drop of bosentan (5 mg/mL, n = 6) or vehicle (n = 6) administered twice daily for 14 days. Six non-diabetic (db/+) mice matched by age were included as the control group. Glial activation was evaluated by immunofluorescence using specific antibodies against glial fibrillary acidic protein (GFAP). Apoptosis was assessed by TUNEL method. A pharmacokinetic study was performed in rabbits. We found that topical administration of bosentan resulted in a significant decrease of reactive gliosis and apoptosis. The results of the pharmacokinetic study suggested that bosentan reached the retina through the trans-scleral route. We conclude that topical administration of bosentan was effective in preventing neurodegeneration in the diabetic retina and, therefore, could be a good candidate to be tested in clinical trials.
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BOGDANOV, Patricia, SIMÓ SERVAT, Olga, SAMPEDRO, Joel, SOLÀ ADELL, Cristina, GARCIA-RAMÍREZ, Marta, RAMOS, Hugo, GUERRERO, Marta, SUÑÉ I NEGRE, Josep m. (josep maria), TICÓ GRAU, Josep r., MONTORO RONSANO, José bruno, DURÁN, Vicente, ARIAS BARQUET, Lluís, HERNÁNDEZ-MUNAIN, Cristina, SIMÓ, Rafael. Topical administration of bosentan prevents retinal neurodegeneration in experimental diabetes. _International Journal of Molecular Sciences_. 2018. Vol. 19, núm. 11, pàgs. 3578. [consulta: 20 de gener de 2026]. ISSN: 1661-6596. [Disponible a: https://hdl.handle.net/2445/159017]