Abstract
Purpose: :
For retinal degeneration, acquired form exemplified by age-related macular degeneration (AMD) and inherited form such as retinitis pigmentosa, there is no cure for such major retinal diseases. The focus of this study was to utilize a newly developed stem cell-based gene therapy for a Sodium Iodate (SI)-induced retinal degeneration animal model.
Methods: :
The preventive and therapeutic effects on neurosensory retina were investigated after the transplantation of the following cell types, i.e., rat mesenchymal stem cells (rMSCs) alone, erythropoietin gene modified rMSC (EPO-rMSCs) or doxycycline (DOX) controllable erythropoietin expression rMSCs (Tet-on EPO-rMSCs ), into the subretinal spaces of SI treated rats. The rMSCs were isolated from femurs bone marrow aspirates of male adult SD rats, then suspended for neural sphere formation and co-cultured with retinal pigment epithelium (RPE) determination medium for in vitro differentiation. During 1 to 8 weeks after the cell transplantation, the therapeutic effects were determined by fundus examination, fluorescein angiography (FFA) and electroretinogram (ERG), and the transplantation efficiency of donor cells was also examined for their survival, integration, and differentiation into retinal cells.
Results: :
Following the transplantation, CM-DiI labeled or lentiviral-transduced donor cells could be observed scattered in the retina and adopted into RPE morphology. Our data showed that EPO concentration in vitreous and retina of SI treated rats transplanted with EPO-rMSCs and Tet-on EPO-rMSCs were significantly increased, in parallel with the improvement of retinal function as indicated by ERG examination, as early as 8 weeks after the transplantation.
Conclusions: :
Our findings indicate that transplantation of EPO gene modified rMSCs, either EPO-rMSCs or Tet-on EPO-rMSCs, may be a new therapeutic procedure for degenerative retinal diseases because they can support and maintain the functions of RPE and retinal neurons.
Keywords: age-related macular degeneration • gene transfer/gene therapy • retinal pigment epithelium