Current opinion in ophthalmology · 2012
Gene therapy for corneal dystrophies and disease, where are we?
СтатьяПоддержка исследования: вне правительства СШАОбзорНазвание и аннотация: Перевод пока не подготовлен
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Williams Keryn A, Klebe Sonja
Аннотация
PURPOSE OF REVIEW: We assess the studies on vector systems for delivery of transgenes to the cornea that have been published over the last year and summarize new work on the identification of specific transgenes for corneal diseases.
RECENT FINDINGS: Adeno-associated viral vectors are increasingly being successfully applied to the cornea, although transgene expression requires corneal epithelial debridement or intrastromal injection of the vector. Gene delivery platforms based on nanoparticles of chitosan or gold also show promise. Overexpression of vasoinhibin-1 or decorin, or siRNA-mediated blockade of the cannabinoid receptor CB1, can all reduce corneal neovascularization. Overexpression of decorin or matrix metalloproteinase 14 can reduce corneal fibrosis and haze, whereas overexpression of c-Met accelerates the epithelial wound healing. Induction of corneal endothelial cell replication by overexpression of E2F2, p16 or p21 can maintain or even increase corneal endothelial cell density in eye bank corneas. Overexpression of the antiapoptotic transgenes Bcl-xL or p35 significantly enhances corneal endothelial cell survival and reduces apoptosis in stored human corneas.
SUMMARY: Despite a wealth of information on the methods for the delivery of nucleic acids to the human cornea and ever-increasing information on the transgenes with substantial therapeutic potential, gene therapy for corneal disorders has yet to reach the clinic.
RECENT FINDINGS: Adeno-associated viral vectors are increasingly being successfully applied to the cornea, although transgene expression requires corneal epithelial debridement or intrastromal injection of the vector. Gene delivery platforms based on nanoparticles of chitosan or gold also show promise. Overexpression of vasoinhibin-1 or decorin, or siRNA-mediated blockade of the cannabinoid receptor CB1, can all reduce corneal neovascularization. Overexpression of decorin or matrix metalloproteinase 14 can reduce corneal fibrosis and haze, whereas overexpression of c-Met accelerates the epithelial wound healing. Induction of corneal endothelial cell replication by overexpression of E2F2, p16 or p21 can maintain or even increase corneal endothelial cell density in eye bank corneas. Overexpression of the antiapoptotic transgenes Bcl-xL or p35 significantly enhances corneal endothelial cell survival and reduces apoptosis in stored human corneas.
SUMMARY: Despite a wealth of information on the methods for the delivery of nucleic acids to the human cornea and ever-increasing information on the transgenes with substantial therapeutic potential, gene therapy for corneal disorders has yet to reach the clinic.