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Petzold A, Nijland PG, Balk LJ, et al. Visual pathway neurodegeneration winged by mitochondrial dysfunction. Ann Clin Transl Neurol. 2014;2(2):140-50doi: 10.1002/acn3.157.
Petzold, A., Nijland, P. G., Balk, L. J., Amorini, A. M., Lazzarino, G., Wattjes, M. P., Gasperini, C., van der Valk, P., Tavazzi, B., Lazzarino, G., & van Horssen, J. (2015). Visual pathway neurodegeneration winged by mitochondrial dysfunction. Annals of clinical and translational neurology, 2(2), 140-50. https://doi.org/10.1002/acn3.157
Petzold, Axel, et al. "Visual pathway neurodegeneration winged by mitochondrial dysfunction." Annals of clinical and translational neurology vol. 2,2 (2015): 140-50. doi: https://doi.org/10.1002/acn3.157
Petzold A, Nijland PG, Balk LJ, Amorini AM, Lazzarino G, Wattjes MP, Gasperini C, van der Valk P, Tavazzi B, Lazzarino G, van Horssen J. Visual pathway neurodegeneration winged by mitochondrial dysfunction. Ann Clin Transl Neurol. 2015 Feb;2(2):140-50. doi: 10.1002/acn3.157. Epub 2014 Dec 17. PMID: 25750919; PMCID: PMC4338955.
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Ann Clin Transl Neurol. 2015 Feb;2(2):140-50. doi: 10.1002/acn3.157. Epub 2014 Dec 17.

Visual pathway neurodegeneration winged by mitochondrial dysfunction.

Annals of clinical and translational neurology

Axel Petzold, Philip G Nijland, Lisanne J Balk, Angela Maria Amorini, Giacomo Lazzarino, Mike P Wattjes, Claudio Gasperini, Paul van der Valk, Barbara Tavazzi, Giuseppe Lazzarino, Jack van Horssen

Affiliations

  1. Department of Neurology, VU University Medical Center De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands ; Department of Ophthalmology, VU University Medical Center De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands ; Molecular Neuroscience, UCL Institute of Neurology Queen Square, London, WC1N 3BG, United Kingdom ; Moorfields Eye Hospital, Neuro-ophthalmology City Road, London, UK.
  2. Department of Pathology, VU University Medical Center Amsterdam, The Netherlands.
  3. Department of Neurology, VU University Medical Center De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
  4. Institute of Biochemistry and Clinical Biochemistry, Catholic University of Rome Largo F. Vito 1, 00168, Rome, Italy.
  5. Department of Radiology & Nuclear Medicine, VU University Medical Center Amsterdam, The Netherlands.
  6. Department of Neurosciences, S Camillo Forlanini Hospital Circonvallazione Gianicolense 87, 00152, Rome, Italy.
  7. Division of Biochemistry and Molecular Biology, Department of Biology, Geology and Environmental Sciences, University of Catania Viale A. Doria 6, 95125, Catania, Italy.
  8. Molecular Cell Biology and Immunology, VU University Medical Center Amsterdam, The Netherlands.

PMID: 25750919 PMCID: PMC4338955 DOI: 10.1002/acn3.157

Abstract

OBJECTIVES: To test for structural and functional contribution of mitochondrial dysfunction to neurodegeneration in multiple sclerosis (MS). A visual pathway model void of MS lesions was chosen in order to exclude neurodegeneration secondary to lesion related axonotmesis.

METHODS: A single-centre cohort study (230 MS patients, 63 controls). Spectral domain optical coherence tomography of the retina, 3T magnetic resonance imaging of the brain, spectrophotometric assessment of serum lactate levels. Postmortem immunohistochemistry.

RESULTS: The visual pathway was void of MS lesions in 31 patients and 31 age-matched controls. Serum lactate was higher in MS compared to controls (P = 0.029). High serum lactate was structurally related to atrophy of the retinal nerve fiber layer at the optic disc (P = 0.041), macula (P = 0.025), and the macular ganglion cell complex (P = 0.041). High serum lactate was functionally related to poor color vision (P < 0.01), Expanded Disability Status Scale score (R = 0.37, P = 0.041), Guy's Neurological disability score (R = 0.38, P = 0.037), MS walking scale (R = 0.50, P = 0.009), upper limb motor function (R = 0.53, P = 0.002). Immunohistochemistry demonstrated increased astrocytic expression of a key lactate generating enzyme in MS lesions as well as profound vascular expression of monocarboxylate transporter-1, which is involved in lactate transport.

INTERPRETATION: This study provides structural, functional, and translational evidence for visual pathway neurodegeneration in MS related to mitochondrial dysfunction.

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