Please use this identifier to cite or link to this item:
Title: Topical administration of bosentan prevents retinal neurodegeneration in experimental diabetes
Author: 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
Keywords: Retinopatia diabètica
Malalties de la retina
Diabetic retinopathy
Retinal diseases
Issue Date: 13-Nov-2018
Publisher: MDPI
Abstract: 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.
Note: Reproducció del document publicat a:
It is part of: International Journal of Molecular Sciences, 2018, vol. 19, num. 11, p. 3578
Related resource:
ISSN: 1661-6596
Appears in Collections:Articles publicats en revistes (Farmàcia, Tecnologia Farmacèutica i Fisicoquímica)
Articles publicats en revistes (Ciències Clíniques)

Files in This Item:
File Description SizeFormat 
684935.pdf3.48 MBAdobe PDFView/Open

This item is licensed under a Creative Commons License Creative Commons