title: Photoreceptor protection by cardiotrophin-1 in transgenic rats with the rhodopsin mutation s334ter.
abstract: OBJECTIVE
  This work examines the effects of cardiotrophin (CT)-1 on photoreceptor survival in transgenic rats that carry the rhodopsin mutation S334ter.
  
  
  METHODS
  Recombinant CT-1 was injected intravitreally into eyes of heterozygous animals. Photoreceptor survival was analyzed by histology. Phosphorylation of signal transducer and activator of transcription1 (STAT1), STAT3, extracellular signal-regulated kinase (ERK), or Akt was assessed by immunoblot analysis. Localization of phosphorylated STAT3 was determined by immunocytochemistry.
  
  
  RESULTS
  Heterozygous S334ter rats experience rapid photoreceptor degeneration. By postnatal day (PD)20, the outer nuclear layer (ONL) retained only 1 to 2 rows of nuclei compared with 10 to 12 rows in wild-type animals. Repeated administration of CT-1 resulted in significant survival of photoreceptors. At PD20, a CT-1-treated eye (2 micro g/2 micro L every 3 days, starting at PD9) had six to seven rows of nuclei, and the vehicle-treated eyes had only one to two rows. At PD30, eyes treated every 3 days still had five to six rows of nuclei, in contrast to no rows to one row in vehicle-treated eyes. Eyes treated every 4 days retained three to four rows, whereas eyes treated every 5 days had two to three rows. There was a significant increase in phosphorylated STAT1 and -3 in the retina after CT-1 injection. The increase in phosphorylated STAT3 was colocalized with glutamine synthetase, a Müller cell marker, by immunocytochemistry.
  
  
  CONCLUSIONS
  These results indicate that CT-1 promotes photoreceptor survival and that Müller cells probably mediate this effect. They also suggest that sustained delivery of the protein is essential for long-term rescue of photoreceptors.
authors.affiliation: Department of Ophthalmology, University of Pennsylvania, School of Medicine, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Song
authors.forename: Lian
authors.initials: L
authors.lastname: Zhao
authors.forename: Weng
authors.initials: W
authors.lastname: Tao
authors.forename: Alan M
authors.initials: AM
authors.lastname: Laties
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Luo
authors.forename: Rong
authors.initials: R
authors.lastname: Wen
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000627:therapeutic use*; D019610:Cytoprotection / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D015151:Immunoblotting; D007124:Immunoenzyme Techniques; D007267:Injections; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009154:Mutation; D010766:Phosphorylation; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D012162:Retinal Degeneration / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D012243:Rhodopsin / Q000235:genetics*; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism; D014822:Vitreous Body
chemical_list: D016207:Cytokines; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D015534:Trans-Activators; D012243:Rhodopsin; C092073:cardiotrophin 1; C494920:Akt1 protein, rat; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases