title: Genetic ablation of cone photoreceptors eliminates retinal folds in the retinal degeneration 7 (rd7) mouse.
abstract: OBJECTIVE
  Folds or pseudorosettes in the outer retina are commonly observed in animals with genetic, viral, or chemically induced retinal degeneration. This study examined the effect of genetic ablation of cone photoreceptors on the production of retinal folds in two mouse retinopathy models. One is the rd7/rd7 retina, a model of enhanced S-cone syndrome, Goldman-Favre syndrome, and clumped pigmentary retinopathy that is also associated with an approximately twofold excess of S-cones. The other is postnatal day (P)0 N-methyl-N-nitrosourea (MNU) treatment.
  
  
  METHODS
  A transgene that directs cone-specific expression of the diphtheria toxin A chain was used to ablate cone photoreceptors. Retinal folds, numbers of photoreceptors, and numbers of cones were quantified in retina flatmounts or transverse sections, and photoreceptor apoptosis was quantified by immunostaining for activated caspase 3.
  
  
  RESULTS
  Cone ablation by the cone-DTA transgene eliminated folds in the rd7/rd7 retina, whereas chemical ablation of up to 30% of rods (by exposure to MNU at P13) had little or no effect on folds in the rd7/rd7 retina. Cone ablation by the cone-DTA transgene had no effect on retinal folds produced by P0 MNU treatment or on the progressive loss of rod photoreceptors in the rd7/rd7 retina.
  
  
  CONCLUSIONS
  Despite their relatively low abundance, cones play a critical role in retinal folding in the rd7/rd7 retina. The relevant molecular and cellular mechanisms remain to be determined.
authors.affiliation: Department of Molecular Biology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Jichao
authors.initials: J
authors.lastname: Chen
authors.forename: Jeremy
authors.initials: J
authors.lastname: Nathans
mesh_terms: D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D004167:Diphtheria Toxin / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D008297:Male; D008770:Methylnitrosourea / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D017949:Retinal Cone Photoreceptor Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D012162:Retinal Degeneration / Q000235:genetics*; D012164:Retinal Diseases / Q000378:metabolism / Q000517:prevention & control*; D017299:Rod Opsins / Q000378:metabolism; D015293:Transducin / Q000378:metabolism; D019076:Transgenes
chemical_list: D004167:Diphtheria Toxin; D010446:Peptide Fragments; D017299:Rod Opsins; C029795:diphtheria toxin fragment A; C095853:short-wavelength opsin; D008770:Methylnitrosourea; D053148:Caspase 3; D015293:Transducin