TY - JOUR
T1 - Visual pathway neurodegeneration winged by mitochondrial dysfunction.
AU - Petzold, Axel
AU - Nijland, Philip G.
AU - Balk, Lisanne J.
AU - Amorini, Angela Maria
AU - Lazzarino, Giacomo
AU - Wattjes, Mike P.
AU - Gasperini, Claudio
AU - Van Der Valk, Paul
AU - Tavazzi, Barbara
AU - Lazzarino, Giuseppe
AU - Lazzarino, Giacomo
AU - Van Horssen, Jack
PY - 2014
Y1 - 2014
N2 - 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 gan-
glion cell complex (P = 0.041). High serum lactate was functionally related to
color vision (P < 0.01), Expanded Disability Status Scale score (P = 0.041),
Guy’s Neurological disability score (P = 0.037), MS walking scale (P = 0.009),
upper limb motor function (R = 0.53, P = 0.002). Immunohistochemistry dem-
onstrated increased astrocytic expression of a key lactate generating enzyme in
MS lesions as well as profound vascular expression of monocarboxylate trans-
porter-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.
AB - 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 gan-
glion cell complex (P = 0.041). High serum lactate was functionally related to
color vision (P < 0.01), Expanded Disability Status Scale score (P = 0.041),
Guy’s Neurological disability score (P = 0.037), MS walking scale (P = 0.009),
upper limb motor function (R = 0.53, P = 0.002). Immunohistochemistry dem-
onstrated increased astrocytic expression of a key lactate generating enzyme in
MS lesions as well as profound vascular expression of monocarboxylate trans-
porter-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.
KW - mitochondrial dysfunction
KW - multiple sclerosis
KW - visual neurodegeneration
KW - mitochondrial dysfunction
KW - multiple sclerosis
KW - visual neurodegeneration
UR - http://hdl.handle.net/10807/64264
U2 - 10.1002/acn3.157
DO - 10.1002/acn3.157
M3 - Article
SN - 2328-9503
VL - 2015
SP - 1
EP - 11
JO - Annals of Clinical and Translational Neurology
JF - Annals of Clinical and Translational Neurology
ER -