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G. K. Athappilly, J. Guy; Serum Phosphorylated Neurofilament Heavy Chain is a Marker of Axonal Loss in Experimental Optic Neuritis. Invest. Ophthalmol. Vis. Sci. 2010;51(13):642.
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© ARVO (1962-2015); The Authors (2016-present)
To quantitate axonal loss of MOG-specific TCR transgenic mice with optic neuritis using in vivo serum assays of phosphorylated neurofilament heavy chain (pNF-H).Axonal and neuronal loss contribute to persistent deficits and disability in MS and optic neuritis. Neurofilaments are major components of the axonal cytoskeleton that consist of 3 major subunits, a light, medium and heavy chain (NF-L, NF-M and NF-H). They are released into the blood stream with axonal disruption. Thus, serum pNF-H levels may provide a prospective measure of neurodegeneration.
Serum from 14 MOG-specific TCR transgenic mice that develop isolated optic neuritis usually without any other characteristic lesions of EAE in the brain or in the spinal cord and 14 littermates negative for the transgene were assayed for the presence of pNF-H. In vivo measurements of optic nerve and retinal ganglion cell injury were assessed by contrast-enhanced 4. 7 Tesla MRI, optical coherence tomography (OCT) and pattern electroretinograms (PERG).
We found an almost 3-fold elevation in serum pNF-H levels in MOG+ (mean = 1.07 picrograms per milliliter) relative to a mean value of 0.38 for controls. This difference was statistically significant (p = 0.02). PERG amplitudes (left eye) of MOG+ mice were reduced 47% relative to control (p= 0 .0075). OCT revealed optic nerve atrophy in MOG+ mice. Transmission electron microscopy revealed loss and apoptosis of RGCs and axons in MOG+ mice, but not in controls. 2D DIGE of the optic nerves revealed a 3 fold reduction in neurofilaments of MOG+ mice relative to MOG-littermates. Histopathology of the spinal cord was normal.
Elevated serum pNF-H levels are a useful biomarker of axonal loss in isolated experimental optic neuritis. This finding suggests that the elevated pNF-H levels described in patients with optic neuritis and MS who had a poor visual outcome are likely also due to axonal demise.
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