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 c subunit of NSE.RESULTS. Serum NSE concentrations in carriers (27.17 6 39.82 lg/L) were significantly higher than affected (5.66 6 4.19 lg/ L; P ¼ 0.050) and off-pedigree controls (6.20 6 2.35 lg/L; P ¼ 0.047). Of the 14/46 (30.4 %) carriers with significantly elevated NSE levels (mean ¼ 75.8 6 42.3 lg/L), 9/14 (64.3%) were male. Furthermore, NSE levels were nearly three times greater in asymptomatic male carriers (40.65 6 51.21 lg/L) than in asymptomatic female carriers (15.85 6 22.27 lg/L; P ¼ 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. (Invest Ophthalmol Vis Sci.

Mitochondrial optic neuropathies: our travels from bench to bedside and back again

“…Many of these subclinical findings, including evidence on the ophthalmoscopy of regional optic disc oedema and telangiectasias, wax and wane but sometimes crescendo, become part of the process of conversion to affected status . These subclinical findings, in connection with biomarkers such as phosphorylated neurofilament heavy chain and neuron‐specific enolase, may be an important metrics in measuring the effects of purported treatments. These observations allow us to address question 2 (the problem of sudden onset). Certain environmental factors may add to the already impaired bioenergetics and reactive oxygen species (ROS) overproduction documented in LHON cells, impinging on the maintenance of mitochondrial membrane potential to the point where a threshold effect occurs and the mitochondrial permeability transition pore (MPTP) opens .…”

“…Many of these subclinical findings, including evidence on the ophthalmoscopy of regional optic disc oedema and telangiectasias, wax and wane but sometimes crescendo, become part of the process of conversion to affected status. 36 These subclinical findings, in connection with biomarkers such as phosphorylated neurofilament heavy chain 44 and neuron-specific enolase, 45 may be an important metrics in measuring the effects of purported treatments. 6 These observations allow us to address question 2 (the problem of sudden onset).…”

Serum neuron‐specific enolase is elevated as a novel indicator of diabetic retinopathy including macular oedema

“…Studies on the relationship between NSE and retinopathy are limited [10,11]. We previously found that serum NSE was closely connected with diabetic peripheral neuropathy [12].…”

What cost mitochondria? The maintenance of functional mitochondrial DNA within and across generations

“…B 369: 20130438 uniparental inheritance are found in flowering plants, including many agricultural crops (reviewed in [55]) and fungi [56]. Often, mutations that are only detrimental to one sex are hidden, as natural selection will favour compensatory mutations in the nuclear genome [51,[57][58][59].…”