title: Photoreceptor-like cells in transgenic mouse eye.
abstract: OBJECTIVE
  Recent success of rescuing vision by photoreceptor replacement in mouse models of photoreceptor degeneration intensifies the need to identify approaches to generate photoreceptors cells for future replacement therapies. We explored the possibility of whether in the mouse eye photoreceptor-like cells could arise from the RPE experimentally manipulated to express a regulatory gene participating in transcriptional networks leading to photoreceptor genesis during retinal development.
  
  
  METHODS
  Transgenic mice were generated with a DNA construct that would express neurogenin1 from RPE bestrophin-1 promoter or neurogenin3 from RPE65 promoter. Transgenic mice were examined with histology and immunohistology for the presence of photoreceptor-like cells and for the presence of cells that might represent transitional stages in RPE-to-photoreceptor reprogramming. Explant culture of "sclera+choroid+RPE" eyecup was used to examine whether cells with photoreceptor traits could arise from the eyecup derived from transgenic mice.
  
  
  RESULTS
  Transgenic animals showed varied degrees of phenotype manifestation. Approximately 60% of offspring from ∼50% of founders contained photoreceptor-like cells in the subretinal space. These cells expressed photoreceptor proteins recoverin, red opsin, and rhodopsin, and displayed morphologic similarities to photoreceptors. In these eyes, the RPE was maintained. Cells seemingly amid RPE-to-photoreceptor transformation were observed in young and aged mice, suggesting old animals were responsive to the reprogramming scheme. De novo generation of photoreceptor-like cells was detected in "sclera+choroid+RPE" eyecup explants derived from adult animals.
  
  
  CONCLUSIONS
  Our results point to a potential way to generate photoreceptor cells in situ in adult mammalian eyes.
authors.affiliation: Department of Ophthalmology, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama 35294-0019, USA. rtyan@uab.edu
authors.forename: Run-Tao
authors.initials: RT
authors.lastname: Yan
authors.forename: Xiumei
authors.initials: X
authors.lastname: Li
authors.forename: Shu-Zhen
authors.initials: SZ
authors.lastname: Wang
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D000075002:Bestrophins; D018929:Cell Culture Techniques / Q000379:methods*; D005136:Eye Proteins / Q000235:genetics; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D007473:Ion Channels / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics; D020419:Photoreceptor Cells, Vertebrate; D055213:Retinal Pigment Epithelium / Q000166:cytology*; D012590:Sclera
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D000075002:Bestrophins; D005136:Eye Proteins; D007473:Ion Channels; D009419:Nerve Tissue Proteins; C491856:Best1 protein, mouse; C486336:Neurog1 protein, mouse
keywords: mammalian retina; photoreceptors; regeneration; reprogramming