RPE MEDIATED RETINAL GENE THERAPY

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DESCRIPTION (Adapted from applicant's abstract): Inherited disorders affecting the retinal pigment epithelium (RPE) and photoreceptor layers cause blindness in both humans and animals. The research will address the issue of whether gene therapy of a potentially proliferating cell population (RPE) can effect a cure for an inherited disease affecting the RPE and, secondarily, the photoreceptors. Autologous RPE cells will deliver gene products to the retina to treat primary disorders of the RPE. This research is now feasible because of recently-developed surgical techniques that provide access to the subretinal space, and because viral vectors can be used for high efficiency gene transfer to RPE cells. The canine mucopolysaccaridoses (MPS) type VII model offers a unique target tissue for therapy and evaluation, where cone photoreceptor pathology is a secondary result of marked alterations in the chondroitin sulfate turnover in the IPM. Two approaches will be used: (1) ex vivo correction of the RPE followed by cell transplantation into the fellow eye, and (2) direct in situ transduction. Both approaches will be assessed for efficacy by clinical, functional, biochemical, morphological and gene expression techniques. The proposed studies will serve as an experimental model for the development of the technology necessary to use genetically modified RPE to treat primary disorders of photoreceptor cells and/or the RPE.