PURPOSE: To evaluate somatic mitochondrial (mt)DNA mutations in the macula during ageing. METHODS: Ten 30-microm cryostat sections from the macula (foveal and perifoveal regions) and peripheral retina of 14 donors (aged 14-94 years) were cut for cytochrome c oxidase cytochemistry. The photoreceptor layer was microdissected and DNA extracted for 4977-bp mtDNA (mtDNA(4977)) quantification using PCR. Dual cytochemistry for cytochrome c oxidase and succinate dehydrogenase allowed the detection of cytochrome c oxidase-deficient cones. RESULTS: Findings showed a progressive accumulation of mtDNA(4977) from ages 14 to 94 years. From ages 14 to 60 years there was an increase from 0.006% to 0.25%, and from ages 60 to 94 years there was a steeper increase from 0.25% to 5.39%. Counts of cones in the dual-reacted preparations showed more cytochrome c oxidase-deficient cones in the foveal region than elsewhere. CONCLUSIONS: The results show that mitochondrial DNA deletions and cytochrome c oxidase-deficient cones accumulate in the ageing retina, particularly in the foveal region. These defects may contribute to the changes in macular function observed in ageing and age-related maculopathy.
PURPOSE: To evaluate somatic mitochondrial (mt)DNA mutations in the macula during ageing. METHODS: Ten 30-microm cryostat sections from the macula (foveal and perifoveal regions) and peripheral retina of 14 donors (aged 14-94 years) were cut for cytochrome c oxidase cytochemistry. The photoreceptor layer was microdissected and DNA extracted for 4977-bp mtDNA (mtDNA(4977)) quantification using PCR. Dual cytochemistry for cytochrome c oxidase and succinate dehydrogenase allowed the detection of cytochrome c oxidase-deficient cones. RESULTS: Findings showed a progressive accumulation of mtDNA(4977) from ages 14 to 94 years. From ages 14 to 60 years there was an increase from 0.006% to 0.25%, and from ages 60 to 94 years there was a steeper increase from 0.25% to 5.39%. Counts of cones in the dual-reacted preparations showed more cytochrome c oxidase-deficient cones in the foveal region than elsewhere. CONCLUSIONS: The results show that mitochondrial DNA deletions and cytochrome c oxidase-deficient cones accumulate in the ageing retina, particularly in the foveal region. These defects may contribute to the changes in macular function observed in ageing and age-related maculopathy.
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