title: Functional and morphological analysis of the subretinal injection of human retinal progenitor cells under Cyclosporin A treatment.
abstract: OBJECTIVE
  The purpose of this study is to evaluate the functional and morphological changes in subretinal xenografts of human retinal progenitor cells (hRPCs) in B6 mice treated with Cyclosporin A (CsA; 210 mg/l in drinking water).
  
  
  METHODS
  The hRPCs from human fetal eyes were isolated and expanded for transplantation. These cells, with green fluorescent protein (GFP) at 11 passages, were transplanted into the subretinal space in B6 mice. A combination of invasive and noninvasive approaches was used to analyze the structural and functional consequences of the subretinal injection of the hRPCs. The process of change was monitored using spectral domain optical coherence tomography (SDOCT), histology, and electroretinography (ERG) at 3 days, 1 week, and 3 weeks after transplantation. Cell counts were used to evaluate the survival rate with a confocal microscope. ERGs were performed to evaluate the physiologic changes, and the structural changes were evaluated using SDOCT and histological examination.
  
  
  RESULTS
  The results of the histological examination showed that the hRPCs gained a better survival rate in the mice treated with CsA. The SDOCT showed that the bleb size of the retinal detachment was significantly decreased, and the retinal reattachment was nearly complete by 3 weeks. The ERG response amplitudes in the CsA group were less decreased after the injection, when compared with the control group, in the dark-adapted and light-adapted conditions. However, the cone-mediated function in both groups was less affected by the transplantation after 3 weeks than the rod-mediated function.
  
  
  CONCLUSIONS
  Although significant functional and structural recovery was observed after the subretinal injection of the hRPCs, the effectiveness of CsA in xenotransplantation may be a novel and potential approach for increasing retinal progenitor cell survival.
authors.affiliation: Zhongshan Ophthalmic Center, State Key Laboratory of Ophthalmology, Sun Yat-sen University, Guangzhou, China ; Department of Ophthalmology, Schepens Eye Research Institute, Harvard Medical School, Boston, MA.
authors.forename: Rui
authors.initials: R
authors.lastname: Huang
authors.affiliation: Department of Ophthalmology, Schepens Eye Research Institute, Harvard Medical School, Boston, MA.
authors.forename: Petr
authors.initials: P
authors.lastname: Baranov
authors.affiliation: Zhongshan Ophthalmic Center, State Key Laboratory of Ophthalmology, Sun Yat-sen University, Guangzhou, China ; Department of Ophthalmology, Schepens Eye Research Institute, Harvard Medical School, Boston, MA.
authors.forename: Kunbei
authors.initials: K
authors.lastname: Lai
authors.affiliation: Department of Ophthalmology, Schepens Eye Research Institute, Harvard Medical School, Boston, MA.
authors.forename: Xinmei
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Zhongshan Ophthalmic Center, State Key Laboratory of Ophthalmology, Sun Yat-sen University, Guangzhou, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Ge
authors.affiliation: Department of Ophthalmology, Schepens Eye Research Institute, Harvard Medical School, Boston, MA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Young
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D016572:Cyclosporine / Q000494:pharmacology*; D004596:Electroretinography; D005333:Fetus; D017930:Genes, Reporter; D006085:Graft Survival / Q000187:drug effects* / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D061251:Primary Cell Culture; D012160:Retina / Q000166:cytology / Q000187:drug effects* / Q000502:physiology / Q000601:surgery; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D041623:Tomography, Optical Coherence; D014183:Transplantation, Heterologous
chemical_list: D007166:Immunosuppressive Agents; D049452:Green Fluorescent Proteins; D016572:Cyclosporine