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Ygal Rotenstreich, Sapir Kalish, Adi Tzameret, Ifat Sher-Rosenthal, Avraham Treves, Arnon Nagler, Michael Belkin; A novel platform for minimally invasive delivery of cells and therapeutics to the posterior segment. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2039.
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© ARVO (1962-2015); The Authors (2016-present)
One of the major limitations in clinical cellular therapy is the current surgical approach that involves invasive pars plana vitrectomy. A limited amount of cells can be injected and therapeutic effect is restricted to the transplanted area. Here we evaluate a novel minimally invasive posterior eye delivery system by means of injection of cells and therapeutics in a thin layer across the extravascular spaces of the choroid covering 70 percent of the sub retinal pigment epithelium (RPE) surface in a rabbit animal model.
A novel system comprised of a syringe with a blunt needle and an adjustable pin was developed. New Zealand White Rabbits (n=12) were injected with human cells and 3 rabbits were injected with near infra-red (NIR) human serum albumin (HSA) core-shell iron oxide nanoparticles (IO/HSANs) of very narrow size distribution (15-200 nm). No immunosuppressants were used. The efficacy of technique and safety profile, were determined using Optical Coherence Tomography (OCT), Electroretinogram (ERG) and histopathology.
Transplanted cells and injected nanoparticles were identified as a thin layer across the extravascular spaces of the choroid, covering 70 percent of the sub RPE surface. Cells and nanoparticles could be identified in the posterior eye up to 2 weeks following injection. OCT scans revealed no retinal detachment or choroidal hemorrhage. No changes in retinal functions were recorded in rabbits following injection. Histopathology demonstrated normal anatomy with no signs of inflammation up to 2 weeks post injection.
Targeting cells and pharmaceuticals to the posterior segment can be achieved using a novel injection platform in a safe and reproducible manner. Therapeutics and cells are placed in close proximity to the RPE and retina as a thin layer, across the extravascular spaces of the choroid without insertion of surgical instruments under the macula, with no retinal detachment or choroidal hemorrhage. This new transplantation system is predicated to increase the therapeutic effect and safety of cell-based therapies and pharmaceuticals for a wide variety of macular and retinal diseases.
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