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Jorge Ricardo Polanco, Rebecca J Kapphahn, Sandra Rocio Montezuma, Deborah A. Ferrington; Altered mitochondrial homeostasis with AMD progression. Invest. Ophthalmol. Vis. Sci. 2018;59(9):341.
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Mitochondrial (mt) damage occurs in the retinal pigment epithelium (RPE) with age-related macular degeneration (AMD). We tested the hypothesis that failure in processes associated with mt maintenance may be responsible for the increased damage observed with AMD progression.
The stage of AMD in donor eyes was determined using the Minnesota Grading System (MGS). Protein was extracted from RPE tissue for donors (ages 48-103 yrs) without AMD (MGS1, n=10) and with AMD (MGS2 early AMD n=5 and MGS3 intermediate AMD n=5). Key proteins that regulate maintenance of mt biogenesis (PGC1α, TFAM), fission/fusion (FIS1, DRP1, MFN1/2, OPA1) and mt autophagy (Parkin) were analyzed using Western immunoblotting. Protein content was compared between the samples utilizing One-way ANOVA and the appropriate post-hoc test.
Decreased content of multiple proteins was observed with AMD progression. FIS1 and Parkin were significantly lower in MGS3 compared to MGS1 donors (p=0.024, 0.024). FIS1, OPA1, and Parkin were lower in MGS3 compared to MGS2 (p=0.038, 0.019, 0.031). TFAM also had a four-fold decrease between MGS2 and MGS3 (p=0.058). In contrast, OPA1 was increased in MGS2 compared to MGS1 (p=0.036).
Proteins that are vital for maintaining mt homeostasis exhibited altered abundance throughout the progression of AMD. Our results suggest these key processes are disrupted and may contribute to the observed AMD-associated mt damage.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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