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Mandeep Singh, Peter Charbel Issa, Alun R. Barnard, Daniel M. Lipinski, Qisheng You, Robert E. MacLaren; Photoreceptor Transplantation Can Restore Vision To The Totally Degenerate Retina. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2238.
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Previous reports have shown that photoreceptor precursor cells may be transplanted into the retina of mice which have a relatively well-formed outer nuclear layer and before significant degeneration. For clinical applications however cell-based therapies are likely to be applied in late stage retinitis pigmentosa when there is marked outer retinal degeneration. We therefore sought to assess the potential for functional repair of the degenerate retina by subretinal transplantation of photoreceptor precursors into the rd mouse in the end stages of retinal degeneration.
Retinal cells were harvested from transgenic nrl-gfp+/+ mice (P3-5) that express green fluorescent protein (GFP) in rods and transplanted into the subretinal space of 10-12 week old rd mice (n=12). A second group of rd mice (n=9) received dissociated retinae from rd mice as a non-rod transplantation control and a third group of rd mice (n=7) acted as uninjected controls. In each group pupillometry curves were generated before and two weeks after transplantation. Pupil areas were compared using paired t-tests with Bonferroni correction. The morphology of transplanted cells was assessed by confocal microscopy.
Two weeks after subretinal transplantation, the pupil response compared to baseline at the median illluminance (1.2 x 1015 photons/m2/s) had improved significantly in animals that received precursor cell transplantation (p<0.00001). No significant improvement was seen in uninjected controls (p=0.23), but there was a borderline improvement seen in sham (non-rod) injected animals (p=0.03). Histology confirmed GFP+ve rod precursor donor cells aligned in the subretinal space of the host, with interconnecting processes connecting donor cells with the host inner retinal architecture.
Transplanted rod precursor cells can integrate into the residual inner nuclear layer of the totally degenerate retina. The pupil response was significantly better two weeks after transplantation, but the presence of a small functional improvement in the sham injected group suggests that the effects are at least in part non-rod related, possibly mediated by transplanted cones or via stimulatory effects on the residual host retinal cells.
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