title: Investigating mitochondria as a target for treating age-related macular degeneration.
abstract: Age-related macular degeneration (AMD) is the leading cause of blindness among older adults in the developed world. Although the pathological mechanisms have not been definitively elucidated, evidence suggests a key role for mitochondrial (mt) dysfunction. The current study used our unique collection of human retinal samples graded for the donor's stage of AMD to address fundamental questions about mtDNA damage in the retina. To evaluate the distribution of mtDNA damage in the diseased retina, damage in the retinal pigment epithelium (RPE) and neural retina from individual donors were compared. To directly test a long-held belief that the macula is selectively damaged with AMD, RPE mtDNA damage was measured in the macula and peripheral sections from individual donors. Small segments of the entire mt genome were examined to determine whether specific regions are preferentially damaged. Our results show that mtDNA damage is limited to the RPE, equivalent mtDNA damage is found in the macular and peripheral RPE, and sites of damage are localized to regions of the mt genome that may impact mt function. These results provide a scientific basis for targeting the RPE mitochondria with therapies that protect and enhance mt function as a strategy for combating AMD.
authors.affiliation: Department of Ophthalmology and Visual Neurosciences, and.
authors.forename: Marcia R
authors.initials: MR
authors.lastname: Terluk
authors.affiliation: Department of Ophthalmology and Visual Neurosciences, and.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Kapphahn
authors.affiliation: University of St Thomas, St Paul, Minnesota 55105.
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Soukup
authors.affiliation: Department of Ophthalmology and Visual Neurosciences, and.
authors.forename: Hwee
authors.initials: H
authors.lastname: Gong
authors.affiliation: Graduate Program in Pharmacology, University of Minnesota, Minneapolis, Minnesota 55455, and.
authors.forename: Christopher
authors.identifier: http://orcid.org/0000-0003-0087-4122
authors.initials: C
authors.lastname: Gallardo
authors.affiliation: Department of Ophthalmology and Visual Neurosciences, and.
authors.forename: Sandra R
authors.initials: SR
authors.lastname: Montezuma
authors.affiliation: Department of Ophthalmology and Visual Neurosciences, and ferri013@umn.edu.
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Ferrington
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism* / Q000473:pathology; D004272:DNA, Mitochondrial / Q000378:metabolism; D016503:Drug Delivery Systems / Q000639:trends; D005260:Female; D018390:Gene Targeting / Q000639:trends; D006801:Humans; D008268:Macular Degeneration / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D055213:Retinal Pigment Epithelium / Q000378:metabolism* / Q000473:pathology
chemical_list: D004272:DNA, Mitochondrial
keywords: age-related macular degeneration; mitochondria; mitochondrial DNA; oxidative damage; retina; retinal pigment epithelium