Neuron-specific enolase is elevated in asymptomatic carriers of Leber's hereditary optic neuropathy

Abstract

Purpose: 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.

Figure 1.

NSE concentration [NSE] and age in subclinical LHON carriers. Thirty-two (70%) of 46 carriers had [NSE] lower than 20 μg/L. Of carriers with [NSE] higher than 20 μg/L, 9 (64%) of 14 were males, and of those with [NSE] higher than 100 μg/L, all (5/5) were male.

Figure 2.

The average of NSE concentration divided by the patient's age in years. The NSE index is the patient's serum NSE concentration divided by his or her age in years. The average NSE index was four times greater in males (1.98) than in females (0.49) with P = 0.02. The SE was 0.15 and 0.67 in females and males, respectively.