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Publication : Severe, early axonal degeneration following experimental anterior ischemic optic neuropathy.

First Author  Lee GH Year  2014
Journal  Invest Ophthalmol Vis Sci Volume  55
Issue  11 Pages  7111-8
PubMed ID  25249599 Mgi Jnum  J:230188
Mgi Id  MGI:5755738 Doi  10.1167/iovs.14-14603
Citation  Lee GH, et al. (2014) Severe, early axonal degeneration following experimental anterior ischemic optic neuropathy. Invest Ophthalmol Vis Sci 55(11):7111-8
abstractText  PURPOSE: 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 mum or 6 +/- 0 enlargements/100 mum. 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 mum or 5.8 +/- 0.4 annexin-V-A488(+) fragments/100 mum, 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.
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