Investigating mitochondria as a target for treating age-related macular degeneration

Marcia R. Terluk, Becky Kapphahn, Lauren M. Soukup, Hwee Gong, Christopher Gallardo, Sandra Rocio Montezuma, Deborah A Ferrington

Research output: Contribution to journalArticle

77 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)7304-7311
Number of pages8
JournalJournal of Neuroscience
Volume35
Issue number18
DOIs
StatePublished - May 6 2015

Fingerprint

Retinal Pigment Epithelium
Macular Degeneration
Mitochondrial DNA
Mitochondria
Retina
Mitochondrial Genome
Blindness

Keywords

  • Age-related macular degeneration
  • Mitochondria
  • Mitochondrial DNA
  • Oxidative damage
  • Retina
  • Retinal pigment epithelium

Cite this

Investigating mitochondria as a target for treating age-related macular degeneration. / Terluk, Marcia R.; Kapphahn, Becky; Soukup, Lauren M.; Gong, Hwee; Gallardo, Christopher; Montezuma, Sandra Rocio; Ferrington, Deborah A.

In: Journal of Neuroscience, Vol. 35, No. 18, 06.05.2015, p. 7304-7311.

Research output: Contribution to journalArticle

Terluk, Marcia R. ; Kapphahn, Becky ; Soukup, Lauren M. ; Gong, Hwee ; Gallardo, Christopher ; Montezuma, Sandra Rocio ; Ferrington, Deborah A. / Investigating mitochondria as a target for treating age-related macular degeneration. In: Journal of Neuroscience. 2015 ; Vol. 35, No. 18. pp. 7304-7311.
@article{63ed4e2eeef3439c8febc0e82c9d8efd,
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.",
keywords = "Age-related macular degeneration, Mitochondria, Mitochondrial DNA, Oxidative damage, Retina, Retinal pigment epithelium",
author = "Terluk, {Marcia R.} and Becky Kapphahn and Soukup, {Lauren M.} and Hwee Gong and Christopher Gallardo and Montezuma, {Sandra Rocio} and Ferrington, {Deborah A}",
year = "2015",
month = "5",
day = "6",
doi = "10.1523/JNEUROSCI.0190-15.2015",
language = "English (US)",
volume = "35",
pages = "7304--7311",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "18",

}

TY - JOUR

T1 - Investigating mitochondria as a target for treating age-related macular degeneration

AU - Terluk, Marcia R.

AU - Kapphahn, Becky

AU - Soukup, Lauren M.

AU - Gong, Hwee

AU - Gallardo, Christopher

AU - Montezuma, Sandra Rocio

AU - Ferrington, Deborah A

PY - 2015/5/6

Y1 - 2015/5/6

N2 - 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.

AB - 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.

KW - Age-related macular degeneration

KW - Mitochondria

KW - Mitochondrial DNA

KW - Oxidative damage

KW - Retina

KW - Retinal pigment epithelium

UR - http://www.scopus.com/inward/record.url?scp=84929353725&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84929353725&partnerID=8YFLogxK

U2 - 10.1523/JNEUROSCI.0190-15.2015

DO - 10.1523/JNEUROSCI.0190-15.2015

M3 - Article

C2 - 25948278

AN - SCOPUS:84929353725

VL - 35

SP - 7304

EP - 7311

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 18

ER -