Gene therapy for corneal dystrophies and disease, where are we?
Williams, Keryn Anne
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We assess studies on vector systems for delivery of transgenes to the cornea that have been published over the last year, and summarise new work on the identification of specific transgenes for corneal diseases. Recent findings Adeno-associated viral vectors (AAV) 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. Over-expression of vasoinhibin-1 or decorin, or siRNA-mediated blockade of the cannabinoid receptor CB1, can all reduce corneal neovascularization. Over-expression of decorin or matrix metalloproteinase 14 can reduce corneal fibrosis and haze, while over-expression of c-Met accelerates epithelial wound healing. Induction of corneal endothelial cell replication by over-expression of E2F2, p16 or p21 can maintain or even increase corneal endothelial cell density in eye bank corneas. Over-expression of the anti-apoptotic 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 methods for the delivery of nucleic acids to the human cornea, and ever-increasing information transgenes with substantial therapeutic potential, gene therapy for corneal disorders has yet to reach the clinic.