title: Functional and cellular responses in a novel rodent model of anterior ischemic optic neuropathy.
abstract: OBJECTIVE
  Anterior ischemic optic neuropathy (AION) is caused by sudden loss of vascular supply to retinal ganglion cell (RGC) axons in the anterior portion of the optic nerve and is a major cause of optic nerve dysfunction. There has been no easily obtainable animal model of this disorder. The current study was conducted to design a novel model of rodent AION (rAION), to enable more detailed study of this disease.
  
  
  METHODS
  A novel rodent photoembolic stroke model was developed that is directly analogous to human AION. Using histologic, electrophysiological, molecular- and cell biological methods, the early changes associated with isolated RGC axonal ischemia were characterized.
  
  
  RESULTS
  Functional (electrophysiological) changes occurred in RGCs within 1 day after rAION, with a loss of visual evoked potential (VEP) amplitude that persisted in the long term. The retinal gene expression pattern rapidly changed after rAION induction, with an early (<1 day) initial induction of c-Fos mRNA, and loss of RGC-specific gene expression. RGC-specific protein expression declined 2 days after detectable mRNA level changes, and immunostaining suggested that multiple retinal layers react to isolated RGC axonal ischemia.
  
  
  CONCLUSIONS
  rAION rapidly results in electrophysiological and histologic changes similar to clinical AION, with reactive responses in primary and supporting neuronal cell layers. The rAION model can enable a detailed analysis of the individual retinal and optic nerve changes that occur after optic nerve stroke, which may be useful in determining possible therapeutic interventions for this disorder.
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D004195:Disease Models, Animal; D005074:Evoked Potentials, Visual / Q000502:physiology*; D005786:Gene Expression Regulation; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics; D018398:Homeodomain Proteins; D007124:Immunoenzyme Techniques; D008297:Male; D018917:Optic Neuropathy, Ischemic / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D016133:Polymerase Chain Reaction; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012164:Retinal Diseases / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D012165:Retinal Ganglion Cells / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D017299:Rod Opsins / Q000096:biosynthesis / Q000235:genetics; D050820:Transcription Factor Brn-3B; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D018398:Homeodomain Proteins; C107835:Hspca protein, mouse; C085559:Pou4f2 protein, mouse; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D017299:Rod Opsins; D050820:Transcription Factor Brn-3B; D014157:Transcription Factors; C081884:heat-shock protein 70.1