The pathophysiology and clinical symptoms observed in adOA show overlap with those occurring in Leber hereditary optic neuropathy,
34 caused by mutations in mtDNA-encoded genes for subunits of complex I of the respiratory chain.
35 Therefore, it is tempting to speculate that mutations in
OPA1 leading to disturbances of mitochondrial integrity may compromise the energy supply to the highly energy-demanding optic nerve tissue, so that it degenerates and visual impairment ensues. Delettre et al.
15 reported that the mitochondrial network is disorganized in leukocytes from patients with
OPA1. Their micrograph of control leukocytes immunostained with anti-HSP60 showed general cytoplasmic staining with no evidence of a mitochondrial network, whereas the antibody seemed to reveal clumps of mitochondria in patients’ cells. Our results are very different. Instead of a general cytoplasmic staining of control leukocytes, we clearly observed a discrete mitochondrial network in the cytosol with the mitochondrion-selective dye
(Fig. 3) and with an antibody against cytochrome
c oxidase subunit I (data not shown). Patients’ cells showed a mitochondrial network that was indistinguishable from that of normal individuals and, moreover, similar to the results reported by Delettre et al.
15 Blood monocytes and granulocytes have extra-large nuclei, folded and lobed, respectively, that leave little room for the cytoplasm in these cells. We thus believe that the distribution of mitochondria observed in patients by both groups, actually represents the typical pattern expected for normal blood monocytes. Therefore, we conclude that these
OPA1 mutations have no observable effect on the mitochondrial distribution in leukocytes. The contradictory results of Delettre et al.
15 could in part be explained by the fact that different patients and mutations were studied but are more likely due to differences in methodology. The absence of any mitochondrial network in their control cells suggests that the cellular structures were not properly fixed before antibody incubation. If adOA caused by
OPA1 mutations is a mitochondriopathy, our findings failed to provide evidence that the disease is readily observable in patients’ leukocytes. Either the mitochondrial abnormalities are limited to the cells of the retinal ganglion cell layer or optic nerve or are more subtle than our methods can detect. Systematic characterization of mitochondria staining patterns across a more comprehensive array of patient
OPA1 mutations and control individuals is warranted to clarify this issue. Nevertheless, we conclude that diagnosis of adOA based on mitochondrial morphology or distribution in blood leukocytes is currently inadvisable.