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Y. Inoue, A. Iriyama, H. Takahashi, Y. Yanagi, S. Ueno, M. Kondo, M. Aihara, Y. Tamaki, M. Araie; Subretinal Transplantation of Bone Marrow Stromal Stem Cells Delays Retinal Degeneration in Royal College of Surgeon Rats . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1418.
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© ARVO (1962-2015); The Authors (2016-present)
To evaluate the protective effect of the subretinal transplantation of bone marrow stromal stem cells using an animal model of retinitis pigmentosa.
Bone marrow stromal stem cells were obtained by Dexter culture from mice. The bone marrow stromal cells or the vehicle (phosphate buffered saline) were transplanted into subretinal space of the left and right eyes, respectively, of 4–week–old Royal College of Surgeon (RCS) rats. At 2, 4 and 8 week after the transplantation, eyes were enucleated and paraffin–sectioned at 4µm. Histologically, the degree of retinal degeneration was assessed by counting the surviving photoreceptor nuclei. Electroretinograms (ERGs) were elicited by Ganzfeld stimuli at 5 and 8 weeks after the subretinal injection to evaluate the retinal function. For statistical analysis, ERG was classified as follows; stage1: characterized by a–wave amplitude attenuation; stage2: marked loss of b–wave amplitude; stage 3: loss of a– and b– wave with oscillatory potential retained; stage4: prominent negative wave becomes apparent; stage 5: negative wave diminishes; stage 6 the wave becomes flat. Mann–Whitney's U test was used to evaluate the difference between the injected eyes and control.
Histologically, the eyes with bone marrow stromal stem cells transplant had significantly greater number of photoreceptor cells than the control eyes at 4 and 8 week after the transplantation (p=0.0122 and 0.0009, at 4 and 8 week, respectively), although number of photoreceptor cells was not different between the transplanted and control eyes at 2 weeks after transplantation. The ERG b–wave was undetectable in all control eyes at 5 weeks after transplantation, whereas it was clearly detected in 3 of 6 eyes in transplanted eyes. In addition, at 8 weeks after transplantation, transplanted eyes had larger ERG responses compared to control eyes. Statistical analysis revealed that, at both 5 and 8 weeks, the injected eyes retained significantly better ERG function (p=0.0063 and 0.0214, at 5 and 8 week, respectively), suggesting that the retinal function of the transplanted eyes with bone marrow stromal stem cells was more preserved than that of control eyes.
Transplantation of bone marrow stromal stem cells into the subretinal space delays the retinal degeneration in RCS rats as revealed by histological and functional analysis. The bone marrow stromal stem cells may have a potential to treat retinitis pigmentosa.
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