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MARCIA TERLUK, Lauren Soukup, Sandra Montezuma, Deborah Ferrington; Mitochondrial DNA Damage Increases with Age-related Macular Degeneration in the RPE but not Neural Retina. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5000.
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Reports of increased mitochondrial DNA (mtDNA) damage in the retinal pigment epithelium (RPE) from human donors with age-related macular degeneration (AMD) provide compelling evidence supporting the hypothesis that mitochondrial dysfunction plays a prominent role in AMD pathology (Karunadharma et al., 2010; Lin et al., 2011). However, it is still not clear whether this damage is limited to the RPE or if it also involves the neural retina. The purpose of this study was to determine if (1) mtDNA damage increases in the neural retina with AMD, and (2) the extent of mtDNA damage in the RPE correlates with the extent of damage in the neural retina in individual donors.
Human donor eyes were obtained from the Minnesota Lions Eye Bank, Minneapolis, MN. Genomic DNA was isolated from a 5 mm trephine punch of the macular region of the RPE and neural retina from human donor eyes categorized into four progressive stages of AMD (MGS 1-4, Olsen and Feng, 2003). Mitochondrial DNA damage was assessed in 32 donors (n=8/stage) using the long extension polymerase chain reaction. In this assay, decreased amplification reflects increased DNA damage. The amplified product was quantified using Pico Green fluorescent dye. Statistical analysis included one way ANOVA and Tukey’s post-hoc tests to determine if there was a significant increase in mtDNA damage with AMD progression. Pearson Product-Moment Correlation analysis was performed comparing the extent of damage in the RPE and retina for each donor to determine if there was an association between damage in these two ocular regions.
There was no significant change in mtDNA damage in the macula of the neural retina when comparing age-matched controls and donors with AMD (p=0.29). Furthermore, comparison of mtDNA damage in the RPE and retina from individual donors showed no correlation (Pearson’s r=0.03; p>0.10) between the extent of mtDNA damage in these two macular tissues.
Collectively our data indicates that mtDNA damage that increases with AMD is limited to the RPE and not the retina. These results suggest that targeting treatments that protect the mitochondria in the RPE may be the most efficacious therapeutic strategy for AMD.
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