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Edward Rickie Chu, Fred N Ross-Cisneros, Anh Hoang Pham, Jesse Gale, Milton Moraes, Solange Rios Salomao, Adriana Berezovsky, Valerio Carelli, Rubens Belfort, Jr., Alfredo A Sadun; The mt11778/ND4 mutation, in Leber’s hereditary optic neuropathy, is associated with less degeneration in the peripheral nerve compared to the mt3460/ND1 mutation. Invest. Ophthalmol. Vis. Sci. 2014;55(13):6208.
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We previously demonstrated peripheral nerve degeneration in Leber’s hereditary optic neuropathy (LHON) from the mt3460/ND1 mutation, considered to be the most severe of the frequent mutations (Mnatsakanyan et al., J Neuroophthalmol. 2011;31:6-11). Herein, we assessed histologic findings of a brachial plexus from a LHON mt11778/ND4 patient also compared to age-matched control nerves.
Brachial plexus was obtained at necropsy from a 77-year-old man with LHON carrying the mt11778/ND4 mutation, with no known history of peripheral neuropathy and diabetes. This was compared to three age-matched controls obtained from the tissue bank of the National Disease Research Institute (Philadelphia, PA). There was no history of neurological diseases or diabetes in control nerves. All tissues were fixed by immersion in a buffered aldehyde solution and processed for epon blocks. Semi-thin cross-sections were obtained for histological examination and stained with p-phenylenediamine (PPD) for myelin and examined by light microscopy. Morphometry was performed on five different areas of the plexus at 400x magnification. Degenerated axons were manually identified as dark, homogenous, opaque profiles. A custom ImageJ software macro (NIH, Bethesda, Maryland) was used to quantify total axonal counts and average myelin density per axon in both LHON and control peripheral nerves.
Peripheral nerves from LHON mt11778/ND4 and controls demonstrated scant nonspecific degeneration, attributable to normal aging. This finding was different from our previous study of mt3460/ND1, in which significant degeneration of the peripheral nerve was present (Mnatsakanyan et al., 2011). Interestingly, total axonal counts were markedly greater in LHON compared to the control group (p>0.05), while average myelin density per axon was significantly less (p< 0.05) in LHON compared to controls.
This is the first report to quantitatively describe histologic features of the peripheral nerve in LHON mt11778/ND4 mutation. Unlike mt3460/ND1, there was no appreciable degeneration in this mt11778/ND4, the less severe LHON mutation. However, reduced myelination and increased axonal counts observed in the peripheral nerve (brachial plexus) might reflect compensatory regeneration.
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