Aim: To obtain whole genome expression profile in Leber hereditary optic neuropathy (LHON) patients with the 11778 mitochondrial DNA mutation.
Methods: RNA was extracted from leukocytes and cDNA reverse transcribed and hybridized to Affymetrix Gene Chips. Principle component analysis (PCA) and the Rate monotonic algorithm (RMA) were performed and further analysis applied to genes with a 2-fold expression difference and p < 0.015 between patients and controls.
Results: The gene expression profile of patients with the 11778 mtDNA mutation was significantly different from controls. The most commonly up-regulated genes (n = 137) were found to be related to the cellular transport (13.8%; 19/137) and transcription (12.4%; 17/137). Similarly, the most commonly down-regulated genes (n = 152) were also related to the cellular transport (17.8%; 27/152) and transcription (18.4%; 28/152). None of the 13 mitochondrial coded genes and no structural mitochondrial nuclear-encoded genes were differentially expressed. Interestingly, OPA1 gene was down-regulated in all LHON patients and this may leads to fragmentation of the mitochondrial network, dissipation of the mitochondrial membrane potential, and disorganization of the cristae.
Conclusions: The presence of the 11778 mtDNA mutation resulted in a unique gene expression profile compared to controls. Down-regulation of OPA1 may contribute to the pathogenesis of LHON.