Early alpha-lipoic acid therapy protects from degeneration of the inner retinal layers and vision loss in an experimental autoimmune encephalomyelitis-optic neuritis model

J Neuroinflammation. 2018 Mar 7;15(1):71. doi: 10.1186/s12974-018-1111-y.

Abstract

Background: In multiple sclerosis (MS), neurodegeneration is the main reason for chronic disability. Alpha-lipoic acid (LA) is a naturally occurring antioxidant which has recently been demonstrated to reduce the rate of brain atrophy in progressive MS. However, it remains uncertain if it is also beneficial in the early, more inflammatory-driven phases. As clinical studies are costly and time consuming, optic neuritis (ON) is often used for investigating neuroprotective or regenerative therapeutics. We aimed to investigate the prospect for success of a clinical ON trial using an experimental autoimmune encephalomyelitis-optic neuritis (EAE-ON) model with visual system readouts adaptable to a clinical ON trial.

Methods: Using an in vitro cell culture model for endogenous oxidative stress, we compared the neuroprotective capacity of racemic LA with the R/S-enantiomers and its reduced form. In vivo, we analyzed retinal neurodegeneration using optical coherence tomography (OCT) and the visual function by optokinetic response (OKR) in MOG35-55-induced EAE-ON in C57BL/6J mice. Ganglion cell counts, inflammation, and demyelination were assessed by immunohistological staining of retinae and optic nerves.

Results: All forms of LA provided equal neuroprotective capacities in vitro. In EAE-ON, prophylactic LA therapy attenuated the clinical EAE score and prevented the thinning of the inner retinal layer while therapeutic treatment was not protective on visual outcomes.

Conclusions: A prophylactic LA treatment is necessary to protect from visual loss and retinal thinning in EAE-ON, suggesting that a clinical ON trial starting therapy after the onset of symptoms may not be successful.

Keywords: EAE-ON; Lipoic acid; Multiple sclerosis; Neurodegeneration; Optical coherence tomography; Optokinetic response.

MeSH terms

  • Animals
  • CD3 Complex / metabolism
  • Disease Models, Animal
  • Encephalomyelitis, Autoimmune, Experimental / chemically induced
  • Encephalomyelitis, Autoimmune, Experimental / complications
  • Encephalomyelitis, Autoimmune, Experimental / pathology*
  • Female
  • Glutathione / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Myelin Basic Protein / metabolism
  • Nerve Degeneration / etiology
  • Nerve Degeneration / prevention & control*
  • Nystagmus, Optokinetic / physiology
  • Protein Carbonylation / physiology
  • Retina / pathology*
  • Thioctic Acid / therapeutic use*
  • Tomography, Optical Coherence
  • Vision Disorders / etiology
  • Vision Disorders / prevention & control*
  • Vitamin B Complex / therapeutic use*

Substances

  • CD3 Complex
  • Myelin Basic Protein
  • Vitamin B Complex
  • Thioctic Acid
  • Glutathione