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Editors Selection IGR 13-3
Basic Research: mtDNA mutations and neural function
Comment by Daniel Won-Kyu Ju on:
46171 Increase in mitochondrial DNA mutations impairs retinal function and renders the retina vulnerable to injury, Kong YXG; Van Bergen N; Trounce IA et al., Aging Cell, 2011; 10: 572-583
Aging has been linked to mtDNA mutation- mediated mitochondrial dysfunction in the pathogensis of many neurodegenerative diseases. Although mtDNA mutations have been proposed to alter mitochondrial function and bioenergetics in optic neuropathies, the relationship between accumulation of mtDNA mutations and neural function in aged retina remains unknown. The purpose of the study by Kong et al. (581) was to determine whether increase in mtDNA mutations renders retinal neurons more vulnerable to injury. Using a mouse model expressing a neuron-targeted mutant form of PolG, this study assessed alterations of retinal mitochondrial oxidative phosphorylation (OXPHOS) enzymes, oxidative stress, and age-related retinal function. Further, to determine whether retinal neurons in PolG transgenic mice have greater vulnerability to injury stress, the authors examined retinal functions with dark-adapted electroretinogram following an acute intraocular pressure (IOP) elevation. The authors found that the retinas of 12-month-old PolG transgenic mice have increased levels of mtDNA mutations and decreased mitochondrial OXPHOS protein expression. Further, these transgenic mice showed accelerated loss of retina function. Importantly, the inner retinal pSTR component of retinal function of PolG transgenic mice at 12 months of age was significantly more vulnerable to acute IOP elevation. These findings suggest that accumulation of mtDNA mutations in aged retinal neurons can induce altered mitochondrial respiratory chain function, result in impaired neural function, and in crease neuronal vulnerability to external stress. Therefore, it would be very interesting to investigate whether there is an age-related accumulation of mtDNA mutations in retinal neurons, specifically retinal ganglion cells, in age-related optic neuropathies including glaucoma.
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