Neuron-specific enolase is elevated in asymptomatic carriers of Leber's hereditary optic neuropathy.
OBJECTIVE
Neuron-specific enolase (NSE) is a biomarker for neuronal stress. Leber's hereditary optic neuropathy (LHON) is a mitochondrial disease affecting retinal ganglion cells (RGC). These RGCs and their axons in the retinal nerve fiber layer (RNFL) and optic nerve head may show subclinical pathology in unaffected mutation carriers, or undergo cell death in affected patients. We hypothesize that increased levels of blood NSE may characterize LHON carriers as a biomarker of ongoing RGC stress.


METHODS
Serum was obtained from 74 members of a Brazilian pedigree with LHON carrying the homoplasmic 11778/ND4 mitochondrial DNA mutation. Classified by symptoms and psychophysical metrics, 46/74 patients were unaffected mutation "carriers," 14/74 were "affected," and 14/74 were "off-pedigree" controls. Serum NSE levels were determined by ELISA specific for the γ subunit of NSE.


RESULTS
Serum NSE concentrations in carriers (27.17 ± 39.82 μg/L) were significantly higher than affected (5.66 ± 4.19 μg/L; P = 0.050) and off-pedigree controls (6.20 ± 2.35 μg/L; P = 0.047). Of the 14/46 (30.4 %) carriers with significantly elevated NSE levels (mean = 75.8 ± 42.3 μg/L), 9/14 (64.3%) were male. Furthermore, NSE levels were nearly three times greater in asymptomatic male carriers (40.65 ± 51.21 μg/L) than in asymptomatic female carriers (15.85 ± 22.27 μg/L; P = 0.034).


CONCLUSIONS
Serum NSE levels are higher in LHON carriers compared with affected and off-pedigree individuals. A subgroup of mostly male carriers had significantly elevated serum NSE levels. Thus, male carriers are at higher risk for LHON-related neuronal stress.
Doheny Eye Institute, Department of Ophthalmology, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA.
Kenneth M
KM
Yee
Fred N
FN
Ross-Cisneros
Jeong Goo
JG
Lee
Arlon Bastos
AB
Da Rosa
Solange R
SR
Salomao
Adriana
A
Berezovsky
Rubens
R
Belfort
Filipe
F
Chicani
Milton
M
Moraes-Filho
Jerry
J
Sebag
Valerio
V
Carelli
Alfredo A
AA
Sadun
D058070:Asymptomatic Diseases / Q000453:epidemiology*; D001938:Brazil / Q000453:epidemiology; D004272:DNA, Mitochondrial / Q000235:genetics; D005192:Family Health; D005260:Female; D006801:Humans; D008297:Male; D029242:Optic Atrophy, Hereditary, Leber / Q000453:epidemiology* / Q000235:genetics / Q000378:metabolism*; D010375:Pedigree; D010751:Phosphopyruvate Hydratase / Q000097:blood*; D012307:Risk Factors; D017678:Sex Distribution; D013312:Stress, Physiological / Q000502:physiology
D004272:DNA, Mitochondrial; D010751:Phosphopyruvate Hydratase