Document Detail

Optic nerve inflammation and demyelination in a rodent model of nonarteritic anterior ischemic optic neuropathy.
MedLine Citation:
PMID:  24065807     Owner:  NLM     Status:  MEDLINE    
PURPOSE: Optic nerve (ON) ischemia associated with nonarteric anterior ischemic optic neuropathy (NAION) results in axon and myelin damage. Myelin damage activates the intraneural Ras homolog A (RhoA), contributing to axonal regeneration failure. We hypothesized that increasing extrinsic macrophage activity after ON infarct would scavenge degenerate myelin and improve postischemic ON recovery. We used the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) to upregulate ON macrophage activity, and evaluated GM-CSF's effects after ON ischemia in the NAION rodent model (rAION).
METHODS: Following rAION induction, GM-CSF was administered via intraventricular injection. Retinal ganglion cell (RGC) stereologic analysis was performed 1 month postinduction. The retinae and optic nerve laminae of vehicle- and GM-CSF-treated animals were examined immunohistochemically and ultrastructurally using transmission electron microscopy (TEM). RhoA activity was analyzed using a rhotekin affinity immunoanalysis and densitometry. Isolated ONs were analyzed functionally ex vivo by compound action potential (CAP) analysis.
RESULTS: Rodent NAION produces ON postinfarct demyelination and myelin damage, functionally demonstrable by CAP analysis and ultrastructurally by TEM. Granulocyte-macrophage colony-stimulating factor increased intraneural inflammation, activating and recruiting endogenous microglia, with only a moderate amount of exogenous macrophage recruitment. Treatment with GM-CSF reduced postinfarct intraneural RhoA activity, but did not neuroprotect RGCs after rAION.
CONCLUSIONS: Sudden ON ischemia results in previously unrecognized axonal demyelination, which may have a clinically important role in NAION-related functional defects and recovery. Granulocyte-macrophage colony-stimulating factor is not neuroprotective when administered directly to the optic nerve following ON ischemia, and does not improve axonal regeneration. It dramatically increases ON-microglial activation and recruitment.
Bernard J Slater; Fernandino L Vilson; Yan Guo; Daniel Weinreich; Shelly Hwang; Steven L Bernstein
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural     Date:  2013-12-05
Journal Detail:
Title:  Investigative ophthalmology & visual science     Volume:  54     ISSN:  1552-5783     ISO Abbreviation:  Invest. Ophthalmol. Vis. Sci.     Publication Date:  2013 Dec 
Date Detail:
Created Date:  2013-12-06     Completed Date:  2014-01-30     Revised Date:  2014-06-03    
Medline Journal Info:
Nlm Unique ID:  7703701     Medline TA:  Invest Ophthalmol Vis Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  7952-61     Citation Subset:  IM    
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MeSH Terms
Demyelinating Diseases / etiology*,  metabolism,  pathology
Disease Models, Animal
Granulocyte-Macrophage Colony-Stimulating Factor / biosynthesis
Microglia / metabolism,  ultrastructure
Microscopy, Electron, Transmission
Optic Nerve / metabolism,  pathology*
Optic Neuritis / complications,  metabolism,  pathology*
Optic Neuropathy, Ischemic / complications,  metabolism,  pathology*
Rats, Sprague-Dawley
Retinal Ganglion Cells / metabolism,  ultrastructure
Grant Support
Reg. No./Substance:
83869-56-1/Granulocyte-Macrophage Colony-Stimulating Factor

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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