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Gene Ther ; 18(5): 462-8, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21160532

RESUMO

Once a corneal scar develops, surgical management remains the only option for visual rehabilitation. Corneal transplantation is the definitive treatment for a corneal scar. In addition to the challenges posed by graft rejections and other postoperative complications, the lack of high-quality donor corneas can limit the benefits possible with keratoplasty. The purpose of our study was to evaluate a new therapeutic strategy for treating corneal scarring by targeting collagen deposition. We overexpressed a fibril collagenase (matrix metalloproteinase 14 (MMP14)) to prevent collagen deposition in the scar tissue. We demonstrated that a single and simple direct injection of recombinant adeno-associated virus-based vector expressing murine MMP14 can modulate gene expression of murine stromal keratocytes. This tool opens new possibilities with regard to treatment. In a mouse model of corneal full-thickness incision, we observed that MMP14 overexpression reduced corneal opacity and expression of the major genes involved in corneal scarring, especially type III collagen and α-smooth muscle actin. These results represent proof of concept that gene transfer of MMP14 can reduce scar formation, which could have therapeutic applications after corneal trauma.


Assuntos
Cicatriz/terapia , Córnea/patologia , Técnicas de Transferência de Genes , Metaloproteinase 14 da Matriz/genética , Animais , Opacidade da Córnea/terapia , Dependovirus/genética , Feminino , Vetores Genéticos , Metaloproteinase 14 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Regulação para Cima , Cicatrização
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