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Editors Selection IGR 18-1

Basic Science: Mitochondrial alterations in glaucoma

Comment by Jonathan Crowston on:

Coenzyme Q10 (CoQ10) is present in the inner mitochondrial membrane and is component of the electron transport chain shuttling electrons from complexes I and II to complex III. This is a key step in ATP production by oxidative phosphorylation (OXPHOS). This interesting study demonstrated a significant increase in RGC survival in DBA/2J mice, with inherited glaucoma, that were fed with a CoQ10 diet for six months compared to control animals not fed a supplemented diet. Increased RGC survival was associated with lower astroglial activation at the optic nerve head as well as lower levels of retinal oxidative stress.

Another interesting observation in this study was that retina of untreated DBA/2J mice had increased mitochondrial DNA copy number, increased complex IV levels and transcription factor profiles indicative of upregulated mitochondrial biogenesis in the retina. This points to a possible compensatory mechanism whereby the retina responds to IOP injury by increasing the number of mitochondria, perhaps in response to increased metabolic demand required to undertake repair processes.

This points to a possible compensatory mechanism whereby the retina responds to IOP injury by increasing the number of mitochondria

Interestingly, the CoQ10-fed mice had a muted mitochondrial biogenesis in the retina, despite lower rates of RGC death. A potential explanation for this is that by promoting ATP production CoQ10 obviates the need for mitochondrial biogenesis. The mechanism by which CoQ10 reduced RGC loss in this particular model, however, remains to be determined. A number of studies have pointed to systemic mitochondrial DNA mutations and OXPHOS dysfunction in glaucoma patients. In contrast, the mice used in this study would be expected to have a normal complement of mitochondria (for age). How then does an essential co-factor of OXPHOS promote RGC survival? The authors (indirectly) point to an interesting hypothesis whereby IOP elevation per se might promote mtDNA damage through glutamate excitotoxicity and oxidative stress. This is an area that clearly requires further work but could provide another piece in the jigsaw of our understanding of the pathogenesis of glaucoma optic neuropathy.

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