title: Induced pluripotent stem cells without c-Myc ameliorate retinal oxidative damage via paracrine effects and reduced oxidative stress in rats.
abstract: OBJECTIVE
  To investigate the efficacy and mechanisms of non-c-Myc induced pluripotent stem cell (iPSC) transplantation in a rat model of retinal oxidative damage.
  
  
  METHODS
  Paraquat was intravitreously injected into Sprague-Dawley rats. After non-c-Myc iPSC transplantation, retinal function was evaluated by electroretinograms (ERGs). The generation of reactive oxygen species (ROS) was determined by lucigenin- and luminol-enhanced chemiluminescence. The expression of brain-derived neurotrophic factor, ciliary neurotrophic factor, basic fibroblast growth factor (bFGF), stromal cell-derived factor (SDF)-1α, and CXCR4 was measured by immunohistochemistry and ELISA. An in vitro study using SH-SY5Y cells was performed to verify the protective effects of SDF-1α.
  
  
  RESULTS
  Transplantation of non-c-Myc iPSCs effectively promoted the recovery of the b-wave ratio in ERGs and significantly ameliorated retinal damage. Non-c-Myc iPSC transplantation decreased ROS production and increased the activities of superoxide dismutase and catalase, thereby reducing retinal oxidative damage and apoptotic cells. Moreover, non-c-Myc iPSC transplantation resulted in significant upregulation of SDF-1α, followed by bFGF, accompanied by a significant improvement in the ERG. In vitro studies confirmed that treatment with SDF-1α significantly reduced apoptosis in a dose-dependent manner in SH-SY5Y cells. Most transplanted cells remained in the subretinal space, with spare cells expressing neurofilament M markers at day 28. Six months after transplantation, no tumor formation was seen in animals with non-c-Myc iPSC grafts.
  
  
  CONCLUSIONS
  We demonstrated the potential benefits of non-c-Myc iPSC transplantation for treating oxidative-damage-induced retinal diseases. SDF-1α and bFGF play important roles in facilitating the amelioration of retinal oxidative damage after non-c-Myc iPSC transplantation.
authors.affiliation: 1 Department of Ophthalmology, Taipei City Hospital Zhongxiao Branch , Taipei City, Taiwan .
authors.forename: I-Mo
authors.initials: IM
authors.lastname: Fang
authors.forename: Chang-Hao
authors.initials: CH
authors.lastname: Yang
authors.forename: Shih-Hwa
authors.initials: SH
authors.lastname: Chiou
authors.forename: Chung-May
authors.initials: CM
authors.lastname: Yang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics; D045744:Cell Line, Tumor; D054377:Chemokine CXCL12 / Q000008:administration & dosage / Q000235:genetics; D004195:Disease Models, Animal; D004596:Electroretinography; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000637:transplantation*; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D019899:Paracrine Communication / Q000502:physiology; D010269:Paraquat / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D012164:Retinal Diseases / Q000473:pathology / Q000628:therapy*; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D054377:Chemokine CXCL12; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D010269:Paraquat