NADH-dehydrogenase type-2 suppresses irreversible visual loss and neurodegeneration in the EAE animal model of MS

Venu Talla, Hong Yu, Tsung Han Chou, Vittorio Porciatti, Vince Chiodo, Sanford L. Boye, William W. Hauswirth, Alfred S. Lewin, John Guy

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

To address mitochondrial dysfunction that mediates irreversible visual loss and neurodegeneration of the optic nerve in the experimental autoimmune encephalomyelitis (EAE) animal model of multiple sclerosis (MS), mice sensitized for EAE were vitreally injected with self-complementary adenoassociated virus (scAAV) containing the NADH-dehydrogenase type-2 (NDI1) complex I gene that quickly expressed in mitochondria of almost all retinal ganglion cells (RGCs). Visual function assessed by pattern electroretinograms (PERGs) reduced by half in EAE showed no significant reductions with NDI1. Serial optical coherence tomography (OCT) revealed significant inner retinal thinning with EAE that was suppressed by NDI1. Although complex I activity reduced 80% in EAE was not improved by NDI1, in vivo fluorescent probes indicated mitochondrial oxidative stress and apoptosis of the EAE retina were reduced by NDI1. Finally, the 42% loss of axons in the EAE optic nerve was ameliorated by NDI1. Targeting the dysfunctional complex I of EAE responsible for loss of respiration, mitochondrial oxidative stress and apoptosis may be a novel approach to address neuronal and axonal loss responsible for permanent disability that is unaltered by current disease modifying drugs for MS that target inflammation.

Original languageEnglish
Pages (from-to)1876-1888
Number of pages13
JournalMolecular Therapy
Volume21
Issue number10
DOIs
StatePublished - Oct 1 2013

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NADH Dehydrogenase
Autoimmune Experimental Encephalomyelitis
Multiple Sclerosis
Animal Models
Optic Nerve
Oxidative Stress
Apoptosis
Retinal Ganglion Cells
Optical Coherence Tomography
Fluorescent Dyes
Axons
Retina
Mitochondria
Respiration
Viruses
Inflammation

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine
  • Genetics
  • Drug Discovery
  • Pharmacology

Cite this

NADH-dehydrogenase type-2 suppresses irreversible visual loss and neurodegeneration in the EAE animal model of MS. / Talla, Venu; Yu, Hong; Chou, Tsung Han; Porciatti, Vittorio; Chiodo, Vince; Boye, Sanford L.; Hauswirth, William W.; Lewin, Alfred S.; Guy, John.

In: Molecular Therapy, Vol. 21, No. 10, 01.10.2013, p. 1876-1888.

Research output: Contribution to journalArticle

Talla, Venu ; Yu, Hong ; Chou, Tsung Han ; Porciatti, Vittorio ; Chiodo, Vince ; Boye, Sanford L. ; Hauswirth, William W. ; Lewin, Alfred S. ; Guy, John. / NADH-dehydrogenase type-2 suppresses irreversible visual loss and neurodegeneration in the EAE animal model of MS. In: Molecular Therapy. 2013 ; Vol. 21, No. 10. pp. 1876-1888.
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