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Caihui Jiang, Petr Baranov, Ruilin Wang, Xinmei Zhang, Michael Young; Functional And Anatomic Evaluation Of Human Retinal Progenitor Cells Transplanted Into The Subretinal Space Of Rhodopsin Knockout Mice. Invest. Ophthalmol. Vis. Sci. 2012;53(14):335.
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A leading cause of untreatable blindness is photoreceptor loss due to retinal degenerative diseases or injury. Replacement of photoreceptors has been suggested as a potential therapeutic approach for treatment of retinal degenerative diseases, such as retinitis pigmentosa and age-related macular degeneration. Here we investigate the functional and anatomic results of transplantation of human retinal progenitor cells (hRPCs) into the subretinal space of rhodopsin knockout mice.
hRPCs were isolated from 18 wk gestational age retina and expanded in vitro up to passage 9. Cells were characterized by flow cytometry for expression of progenitor markers. 100,000 live cells were transplanted into the subretinal space of rhodopsin -/- mice in HBSS + N -acetyl-cysteine (NAC). Mice in control group received subretinal injection of HBSS + NAC. Electroretinogram (ERG) and optical coherence tomography (OCT) were performed at various time after transplantation. Mice were sacrificed by CO2 inhalation 4 to 8 weeks after transplantation. Immunohistochemistry study was performed with the following primary antibodies against human mitochondria, nestin, Ki67, rhodopsin, recoverin. Retinal sections were viewed on a confocal microscope.
The b-wave amplitudes of ERG in hRPC treatment group were significantly higher than that in the HBSS + NAC control group. The outer nuclear layers (ONL) of retinas in hRPC treatment group were significantly thicker than that in the HBSS + NAC control groups. 4 to 8 weeks after transplantation, a subset of hRPCs survived as xenografts in the mouse subretinal space without exogenous immune suppression. Grafted hRPCs migrated and incorporated into the recipient neural retina as was confirmed by human mitochondria staining. Integrated cells also express photoreceptor markers rhodopsin and recoverin.
Transplantation of hRPCs restore retinal structure and function in retinal degenerative mice. Transplanted hRPCs migrate and integrate into the mouse retina and differentiate into photoreceptors. These results suggest the potential of hRPC transplantation for treating retinal degenerative diseases.
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