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1.
PLoS One ; 8(8): e70785, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23940641

RESUMO

Corneal scarring remains a major cause of blindness world-wide, with limited treatment options, all of which have side-effects. Here, we tested the hypothesis that topical application of Rosiglitazone, a Thiazolidinedione and ligand of peroxisome proliferator activated receptor gamma (PPARγ), can effectively block scar formation in a cat model of corneal damage. Adult cats underwent bilateral epithelial debridement followed by excimer laser ablation of the central corneal stroma to a depth of ~160 µm as a means of experimentally inducing a reproducible wound. Eyes were then left untreated, or received 50 µl of either 10 µM Rosiglitazone in DMSO/Celluvisc, DMSO/Celluvisc vehicle or Celluvisc vehicle twice daily for 2 weeks. Cellular aspects of corneal wound healing were evaluated with in vivo confocal imaging and post-mortem immunohistochemistry for alpha smooth muscle actin (αSMA). Impacts of the wound and treatments on optical quality were assessed using wavefront sensing and optical coherence tomography at 2, 4, 8 and 12 weeks post-operatively. In parallel, cat corneal fibroblasts were cultured to assess the effects of Rosiglitazone on TGFß-induced αSMA expression. Topical application of Rosiglitazone to cat eyes after injury decreased αSMA expression and haze, as well as the induction of lower-order and residual, higher-order wavefront aberrations compared to vehicle-treated eyes. Rosiglitazone also inhibited TGFß-induced αSMA expression in cultured corneal fibroblasts. In conclusion, Rosiglitazone effectively controlled corneal fibrosis in vivo and in vitro, while restoring corneal thickness and optics. Its topical application may represent an effective, new avenue for the prevention of corneal scarring with distinct advantages for pathologically thin corneas.


Assuntos
Cicatriz/prevenção & controle , Córnea/efeitos dos fármacos , Tiazolidinedionas/administração & dosagem , Actinas/metabolismo , Administração Tópica , Animais , Gatos , Diferenciação Celular , Células Cultivadas , Córnea/patologia , Aberrações de Frente de Onda da Córnea/tratamento farmacológico , Avaliação Pré-Clínica de Medicamentos , Miofibroblastos/efeitos dos fármacos , Miofibroblastos/fisiologia , PPAR gama/agonistas , Rosiglitazona , Fator de Crescimento Transformador beta/fisiologia , Resultado do Tratamento , Cicatrização/efeitos dos fármacos
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