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Editors Selection IGR 15-4

Basic Research: mtDNA deletions in TM

Comment by Jonathan Crowston & Nicole Van Bergen on:

28242 Mitochondrial damage in the trabecular meshwork occurs only in primary open-angle glaucoma and in pseudoexfoliative glaucoma, Izzotti A; Longobardi M; Cartiglia C et al., PLoS ONE, 2011; 6: 14567

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Increased rates of mitochondrial DNA mutations have been identified in a number of age-related neurodegenerative conditions including glaucoma and are thought to contribute to increased neuronal vulnerability to stress. Izzotti et al. (32) now report increased rates of the common mtDNA deletions in trabecular meshwork biopsies harvested during trabeculectomy.

The authors examined DNA from trabecular meshwork biopsies from 38 patients with various types of glaucoma and compared mtDNA deletion rates with a similar aged cohort of samples taken from cadaver controls, who were presumed not to have glaucoma. Although TM cellularity was decreased in all glaucoma samples, increased mtDNA deletions were only observed in biopsies from POAG and pseudoexfoliation samples and not from angle-closure, neovascular, pigmentary, congenital or juvenile glaucoma's. Further, significantly increased levels of oxidative nuclear DNA damage were also seen in POAG and PXF samples but not the other glaucoma subtypes or controls. The screening technique employed, detects the common large scale deletion of mtDNA, which is associated with neuronal aging and increased rates of deletion indicate that either mtDNA maintenance is impaired, or that oxidative stress is driving mtDNA damage.

The authors are to be congratulated for overcoming obvious logistic difficulties in conducting such a study. Use of surgical and cadaveric tissues will inevitably restrict patient numbers and the small trabecular meshwork biopsies provided also precludes comprehensive assessment of oxidative stress and mitochondrial function in these samples. None the less, these results raise the intriguing possibility that mitochondrial dysfunction in glaucoma may contribute not only to optic nerve vulnerability but also predispose to elevated IOP, thus linking anterior and posterior segment pathology in POAG.

Mitochondrial dysfunction in glaucoma may contribute not only to optic nerve vulnerability but also predispose to elevated IOP, thus linking anterior and posterior segment pathology in POAG

As always, interesting findings raise many more questions and it will be fascinating to determine whether the reported changes in TM are primary or secondary to IOP elevation and also how the exfoliation process in PXF is linked to mitochondrial deletions.

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