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Visual pathway neurodegeneration winged by mitochondrial dysfunction.

Axel Petzold1, Philip G Nijland2, Lisanne J Balk3

  • 1Department 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.

Annals of Clinical and Translational Neurology
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Summary
This summary is machine-generated.

Mitochondrial dysfunction contributes to neurodegeneration in multiple sclerosis (MS). Elevated serum lactate in MS patients correlates with structural damage and functional vision loss, indicating a key role in disease progression.

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Area of Science:

  • Neuroscience
  • Ophthalmology
  • Biochemistry

Background:

  • Multiple sclerosis (MS) is a neurodegenerative disease characterized by demyelination and axonal damage.
  • Mitochondrial dysfunction is increasingly implicated in neurodegenerative processes.
  • The visual pathway offers a model to study neurodegeneration independent of MS lesions.

Purpose of the Study:

  • To investigate the structural and functional role of mitochondrial dysfunction in MS neurodegeneration.
  • To assess the contribution of elevated serum lactate to visual pathway damage in MS.

Main Methods:

  • A cohort study involving 230 MS patients and 63 controls.
  • Utilized spectral domain optical coherence tomography (SD-OCT) and 3T MRI for structural assessment.
  • Measured serum lactate levels and performed postmortem immunohistochemistry.

Main Results:

  • Higher serum lactate levels were observed in MS patients compared to controls.
  • Elevated lactate correlated with retinal nerve fiber layer atrophy and ganglion cell complex thinning.
  • High serum lactate was associated with impaired color vision and increased disability scores.

Conclusions:

  • Provides evidence linking mitochondrial dysfunction, indicated by elevated serum lactate, to neurodegeneration in the MS visual pathway.
  • Demonstrates structural and functional deficits associated with high lactate levels.
  • Translational findings suggest lactate metabolism as a potential therapeutic target in MS.