title: Severe, early axonal degeneration following experimental anterior ischemic optic neuropathy.
abstract: OBJECTIVE
  Anterior ischemic optic neuropathy (AION) is the most common acute optic neuropathy in adults older than 50 and leads to axonal degeneration, thinning of the retinal nerve fiber layer and loss of the retinal ganglion cells (RGCs). We used experimental AION model to study early axonal changes following ischemia.
  
  
  METHODS
  We induced optic nerve head ischemia in adult mice using photochemical thrombosis and analyzed retinal changes within 1 week. We used confocal scanning laser ophthalmoscopy (cSLO) and fluorescence microscopy of retinal whole mount preparations to analyze axonal degeneration in Thy1-YFP-H mice and those injected with annexin-V-A488 intravitreally.
  
  
  RESULTS
  Three days after AION, morphometric analyses in Thy1-YFP-H mice revealed evidence of early axonal changes, including swollen or branched axonal stumps. There was also a beads-on-a-string appearance of YFP expression. The axonal enlargements occurred at an interval of 17 ± 1 μm or 6 ± 0 enlargements/100 μm. At day 7 after AION, the degenerating intraretinal RGC axons exhibited intense annexin-V-A488 staining (P = 0.002). The annexin-V staining pattern was fragmented, with intersegment interval of 20.1 ± 1.4 μm or 5.8 ± 0.4 annexin-V-A488(+) fragments/100 μm, which were similar to that of degenerating Thy1-YFP(+) axons.
  
  
  CONCLUSIONS
  Following a photochemical thrombosis model of AION, RGC axons displayed severe degenerative changes within 1 week, suggesting that after ischemia, RGC axons may degenerate in a temporally and spatially distinct fashion from that of the soma. Our findings also further established annexin-V as a useful marker of retinal degeneration because it strongly labeled dying RGC axons.
authors.affiliation: Department of Ophthalmology, Stanford University School of Medicine, Stanford, California, United States.
authors.forename: Gun Ho
authors.initials: GH
authors.lastname: Lee
authors.affiliation: Department of Ophthalmology, Stanford University School of Medicine, Stanford, California, United States.
authors.forename: Madison P
authors.initials: MP
authors.lastname: Stanford
authors.affiliation: Department of Ophthalmology, Stanford University School of Medicine, Stanford, California, United States.
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Shariati
authors.affiliation: Department of Ophthalmology, Stanford University School of Medicine, Stanford, California, United States.
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Ma
authors.affiliation: Department of Ophthalmology, Stanford University School of Medicine, Stanford, California, United States.
authors.forename: Yaping Joyce
authors.initials: YJ
authors.lastname: Liao
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology*; D004195:Disease Models, Animal; D018450:Disease Progression; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D009887:Ophthalmoscopy; D009898:Optic Disk / Q000473:pathology*; D018917:Optic Neuropathy, Ischemic / Q000473:pathology*; D012165:Retinal Ganglion Cells / Q000473:pathology*; D012720:Severity of Illness Index
keywords: AION; RGC; Thy1-YFP; annexin-V; ischemia; ischemic optic neuropathy; optic nerve; retinal ganglion cells