title: Cone degeneration following rod ablation in a reversible model of retinal degeneration.
abstract: OBJECTIVE
  Amphibian retinas regenerate after injury, making them ideal for studying the mechanisms of retinal regeneration, but this leaves their value as models of retinal degeneration in question. The authors asked whether the initial cellular changes after rod loss in the regenerative model Xenopus laevis mimic those observed in nonregenerative models. They also asked whether rod loss was reversible.
  
  
  METHODS
  The authors generated transgenic X. laevis expressing the Escherichia coli enzyme nitroreductase (NTR) under the control of the rod-specific rhodopsin (XOP) promoter. NTR converts the antibiotic metronidazole (Mtz) into an interstrand DNA cross-linker. A visually mediated behavioral assay and immunohistochemistry were used to determine the effects of Mtz on the vision and retinas of XOPNTR F1 tadpoles.
  
  
  RESULTS
  NTR expression was detected only in the rods of XOPNTR tadpoles. Mtz treatment resulted in rapid vision loss and near complete ablation of rod photoreceptors by day 12. Müller glial cell hypertrophy and progressive cone degeneration followed rod cell ablation. When animals were allowed to recover, new rods were born and formed outer segments.
  
  
  CONCLUSIONS
  The initial secondary cellular changes detected in the rodless tadpole retina mimic those observed in other models of retinal degeneration. The rapid and synchronous rod loss in XOPNTR animals suggested this model may prove useful in the study of retinal degeneration. Moreover, the regenerative capacity of the Xenopus retina makes these animals a valuable tool for identifying the cellular and molecular mechanisms at work in lower vertebrates with the remarkable capacity of retinal regeneration.
authors: Department of Ophthalmology, Center for Vision Research, SUNY Eye Institute, Upstate Medical University, Syracuse, NY 13210, USA.
authors: Rene Y
authors: RY
authors: Choi
authors: Gustav A
authors: GA
authors: Engbretson
authors: Eduardo C
authors: EC
authors: Solessio
authors: Georgette A
authors: GA
authors: Jones
authors: Adam
authors: A
authors: Coughlin
authors: Ilija
authors: I
authors: Aleksic
authors: Michael E
authors: ME
authors: Zuber
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis / Q000187:drug effects; D064026:Calbindins; D002452:Cell Count; D004195:Disease Models, Animal; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D005838:Genotype; D017404:In Situ Hybridization, Fluorescence; D020287:In Situ Nick-End Labeling; D008297:Male; D008795:Metronidazole / Q000633:toxicity; D008856:Microscopy, Fluorescence; D009457:Neuroglia / Q000473:pathology; D009601:Nitroreductases / Q000235:genetics / Q000378:metabolism; D012038:Regeneration / Q000502:physiology; D017949:Retinal Cone Photoreceptor Cells / Q000201:enzymology / Q000473:pathology*; D017948:Retinal Rod Photoreceptor Cells / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D012174:Retinitis Pigmentosa / Q000201:enzymology / Q000473:pathology*; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D014786:Vision Disorders / Q000139:chemically induced / Q000473:pathology; D014982:Xenopus laevis
chemical_list: D064026:Calbindins; D029968:Escherichia coli Proteins; D064030:S100 Calcium Binding Protein G; D008795:Metronidazole; C116053:NfsA protein, E coli; D009601:Nitroreductases