Glutathione depletion in antioxidant defense of differentiated NT2-LHON cybrids

The mechanism of retinal ganglion cell loss in Leber's hereditary optic neuropathy (LHON) is still uncertain, and a role of enhanced superoxide production by the mutant mitochondrial complex I has been hypothesized. In the present study, it was shown that LHON cybrids, carrying the np11778 mutation, became selectively more H2O2 sensitive compared with the parental cell line only following short-term retinoic acid differentiation. They contained a decreased cellular glutathione pool (49%, p ≤ 0.05), despite 1.5-fold enhanced expression of the regulatory subunit of γ-glutamylcysteine synthetase (p ≤ 0.05). This points to a reduction of the capacity to detoxify H2O2 and to changes in thiol redox potential. The activity of the H2O2 degrading enzyme glutathione peroxidase (GPx) and the activities of glutathione reductase (GR) and superoxide dismutase (SOD) were unaffected.