Improvement of Photoreceptors Function Following Transplantation of Neurosphere Derived RPE Cells into Subretinal Space of Rat RPE Degeneration Model.
Hamid Aboutaleb kadkhodaeian1 *, Taki Tiraihi2 , Hamid Ahmadieh3 , Hossein Ziaei3 , Narsis Daftarian4 , Taher Taheri5
- Department of Anatomical Sciences, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran.
- Department of Anatomical Sciences, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
- Ophthalmic Research Center, Research Institute for Ophthalmology and Vision Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
- Ocular Tissue Engineering Research Center, Research Institute for Ophthalmology and Vision Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
- Shefa Neuroscience Research Center, Khatam-Alanbia Hospital, Rashid Yasemi Street, Tehran, Iran.
Abstract: To investigate transplantation of pigmented sphere that express RPE antigen(s) (PSRA) in age related macular degeneration model using sodium iodate to rescue and improve a-wave and b-wave activity and outer nuclear layer thickness and cell number.
Methods: AMD model was induced using retro-orbital sodium iodate injection. Cell injection was performed into the subretinal space through the scleral approach. For cell transplantation, rat bone marrow stromal stem cells were differentiated to neurospheres and then into retinal pigment epithelium (RPE) cells. For tracking, the differentiated cells labeled with BrdU and then transplanted into the subretinal space. Photoreceptors function was evaluated in time courses (7-90 days) using full-field electroretinography and effects of transplanted cells on neurosensory retina and RPE layer were assessed using immunohistochemistry and cresyl violet staining.
Results: The data showed that the only effect was on the scotopic b-wave at an intensity of 0.01 cd.s/m2 and photopic a-wave at an intensity of 3.0 cd.s/m2. Significant differences between the test group and the relevant control appeared at 60 days, but only for the scotopic assay and at 90 days for the photopic assay. Further investigation using specific RPE cell protein RPE65 revealed that these cells could express specific proteins as well. There was a significant difference between ONL cells counts in all groups. Similarly, there was a significant difference between ONL thicknesses in all groups.
Conclusion: We demonstrated that PSRA migrated into the subretinal space and integrated into the host layer, and expressed ZO-1, RPE65 markers. Also, we showed that the photoreceptor activity improved, and the ONL cell numbers and thickness were better preserved than in RPE-damaged rats that only received PBS.
