title: Transplantation of reprogrammed embryonic stem cells improves visual function in a mouse model for retinitis pigmentosa.
abstract: BACKGROUND
  To study whether C57BL/6J-Tyr/J (C2J) mouse embryonic stem (ES) cells can differentiate into retinal pigment epithelial (RPE) cells in vitro and then restore retinal function in a model for retinitis pigmentosa: Rpe65/Rpe65 C57BL6 mice.
  
  
  METHODS
  Yellow fluorescent protein (YFP)-labeled C2J ES cells were induced to differentiate into RPE-like structures on PA6 feeders. RPE-specific markers are expressed from differentiated cells in vitro. After differentiation, ES cell-derived RPE-like cells were transplanted into the subretinal space of postnatal day 5 Rpe65/Rpe65 mice. Live imaging of YFP-labeled C2J ES cells demonstrated survival of the graft. Electroretinograms (ERGs) were performed on transplanted mice to evaluate the functional outcome of transplantation.
  
  
  RESULTS
  RPE-like cells derived from ES cells sequentially express multiple RPE-specific markers. After transplantation, YFP-labeled cells can be tracked with live imaging for as long as 7 months. Although more than half of the mice were complicated with retinal detachments or tumor development, one fourth of the mice showed increased electroretinogram responses in the transplanted eyes. Rpe65/Rpe65 mice transplanted with RPE-like cells showed significant visual recovery during a 7-month period, whereas those injected with saline, PA6 feeders, or undifferentiated ES cells showed no rescue.
  
  
  CONCLUSIONS
  ES cells can differentiate, morphologically, and functionally, into RPE-like cells. Based on these findings, differentiated ES cells have the potential for the development of new therapeutic approaches for RPE-specific diseases such as certain forms of retinitis pigmentosa and macular degeneration. Nevertheless, stringent control of retinal detachment and teratoma development will be necessary before initiation of treatment trials.
authors.affiliation: Department of Ophthalmology, Columbia University, New York City, NY, USA.
authors.forename: Nan-Kai
authors.initials: NK
authors.lastname: Wang
authors.forename: Joaquin
authors.initials: J
authors.lastname: Tosi
authors.forename: Jennifer Mie
authors.initials: JM
authors.lastname: Kasanuki
authors.forename: Chai Lin
authors.initials: CL
authors.lastname: Chou
authors.forename: Jian
authors.initials: J
authors.lastname: Kong
authors.forename: Nancy
authors.initials: N
authors.lastname: Parmalee
authors.forename: Katherine J
authors.initials: KJ
authors.lastname: Wert
authors.forename: Rando
authors.initials: R
authors.lastname: Allikmets
authors.forename: Chi-Chun
authors.initials: CC
authors.lastname: Lai
authors.forename: Chung-Liang
authors.initials: CL
authors.lastname: Chien
authors.forename: Takayuki
authors.initials: T
authors.lastname: Nagasaki
authors.forename: Chyuan-Sheng
authors.initials: CS
authors.lastname: Lin
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Tsang
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D048430:Cell Shape; D002470:Cell Survival; D002478:Cells, Cultured; D018920:Coculture Techniques; D004195:Disease Models, Animal; D004596:Electroretinography; D053595:Embryonic Stem Cells / Q000378:metabolism / Q000637:transplantation*; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D008164:Luminescent Proteins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D009154:Mutation; D020127:Recovery of Function; D055213:Retinal Pigment Epithelium / Q000378:metabolism / Q000473:pathology*; D012174:Retinitis Pigmentosa / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D013997:Time Factors; D014162:Transfection; D014785:Vision, Ocular; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase
chemical_list: D015415:Biomarkers; D002352:Carrier Proteins; D005136:Eye Proteins; D008164:Luminescent Proteins; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase