Perspective on AMD Pathobiology: A Bioenergetic Crisis in the RPE

Investigative Ophthalmology & Visual Science
Cody R Fisher, Deborah A Ferrington

Abstract

AMD is the leading cause of blindness in developed countries. The dry form of AMD, also known as atrophic AMD, is characterized by the death of RPE and photoreceptors. Currently, there are no treatments for this form of the disease due in part to our incomplete understanding of the mechanism causing AMD. Strong experimental evidence from studies of human donors with AMD supports the emerging hypothesis that defects in RPE mitochondria drive AMD pathology. These studies, using different experimental methods, have shown disrupted RPE mitochondrial architecture and decreased mitochondrial number and mass, altered content of multiple mitochondrial proteins, increased mitochondrial DNA damage that correlates with disease severity, and defects in bioenergetics for primary RPE cultures from AMD donors. Herein, we discuss a model of metabolic uncoupling that alters bioenergetics in the diseased retina and drives AMD pathology. These data provide the rationale for targeting the mitochondria in the RPE as the most efficacious intervention strategy if administered early, before vision loss and cell death.

References

Jan 21, 1997·Proceedings of the National Academy of Sciences of the United States of America·F M Yakes, B Van Houten
Dec 31, 1998·Archives of Ophthalmology·T IshibashiS J Ryan
Oct 18, 2000·Survey of Ophthalmology·S BeattyM Boulton
Oct 23, 2002·Proceedings of the National Academy of Sciences of the United States of America·John W CrabbJoe G Hollyfield
Nov 13, 2002·Archives of Ophthalmology·Joshua L DunaiefAnn H Milam
Aug 19, 2003·The Journal of Biological Chemistry·Xiaorong GuRobert G Salomon
Sep 29, 2004·Investigative Ophthalmology & Visual Science·Kimberly A HowesWolfgang Baehr
Nov 24, 2004·Investigative Ophthalmology & Visual Science·Timothy W Olsen, Xiao Feng
Dec 8, 2004·Cellular and Molecular Life Sciences : CMLS·M PatrushevA Gaziev
Apr 30, 2005·American Journal of Ophthalmology·Eric A PostelMargaret A Pericak-Vance
Jun 28, 2005·Neurobiology of Aging·Janos FeherCorrado Balacco Gabrieli
Mar 1, 2006·Investigative Ophthalmology & Visual Science·Curtis L NordgaardDeborah A Ferrington
May 26, 2006·Investigative Ophthalmology & Visual Science·Cheryl M EthenDeborah A Ferrington
Feb 7, 2007·American Journal of Ophthalmology·Alejandra DecaniniTimothy W Olsen
Mar 18, 2008·Investigative Ophthalmology & Visual Science·Curtis L NordgaardDeborah A Ferrington
Feb 10, 2009·Molecular & Cellular Proteomics : MCP·Jiayin GuUNKNOWN Clinical Genomic and Proteomic AMD Study Group
May 14, 2009·Molecular & Cellular Proteomics : MCP·Jiaqian NiUNKNOWN Clinical Genomic and Proteomic AMD Study Group
Aug 8, 2009·Annual Review of Genetics·Chunxin Wang, Richard J Youle
Mar 20, 2010·Advances in Experimental Medicine and Biology·Jiayin GuUNKNOWN Clinical Genomic and Proteomic AMD Study Group
May 28, 2010·Investigative Ophthalmology & Visual Science·Pabalu P KarunadharmaDeborah A Ferrington
Jun 12, 2012·PLoS Genetics·Nolan G EricsonJason H Bielas
Jun 26, 2012·Biochimica Et Biophysica Acta·Susan D Cline
Apr 9, 2013·Experimental Eye Research·Vera L BonilhaJoe G Hollyfield
May 30, 2013·Clinical Genetics·R Ratnapriya, E Y Chew
Mar 15, 2014·JAMA Ophthalmology·Alan C BirdGregory S Hageman
Jun 6, 2014·The Journal of Biological Chemistry·Jeffrey AdijantoNancy J Philp
Oct 15, 2014·Proceedings of the National Academy of Sciences of the United States of America·Jiujiu YuTiffany Horng
Mar 25, 2015·Journal of Neuroscience Research·James B HurleyJianhai Du
May 8, 2015·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Marcia R TerlukDeborah A Ferrington
Nov 20, 2015·Oxidative Medicine and Cellular Longevity·Fernanda Marques da CunhaAlicia J Kowaltowski
Feb 9, 2016·Experimental Eye Research·Deborah A FerringtonM Cristina Kenney
Dec 3, 2016·Proceedings of the National Academy of Sciences of the United States of America·Jianhai DuJennifer R Chao
Jan 6, 2017·Cell Death & Disease·Nady GolestanehAlexander C Theos

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Citations

May 22, 2019·The Journal of Biological Chemistry·Michelle YamJianhai Du
Jul 28, 2020·Clinical & Experimental Ophthalmology·Shreya SomasundaranLivia S Carvalho
Dec 24, 2018·Investigative Ophthalmology & Visual Science·Milam A Brantley, James T Handa
Jul 2, 2020·Nature Photonics·T LaforestC Moser
Aug 25, 2020·Translational Vision Science & Technology·Charles WrightSanta J Tumminia
Aug 22, 2020·Translational Vision Science & Technology·Chandima BulumullaKarl G Csaky
Feb 9, 2020·International Journal of Molecular Sciences·Carlota Suárez-BarrioJesús Merayo-Lloves
May 1, 2020·Scientific Reports·Francisco J Valiente-SorianoMarta Agudo-Barriuso
May 22, 2020·Proceedings of the National Academy of Sciences of the United States of America·Shun-Yun ChengClaudio Punzo
Apr 26, 2020·International Journal of Molecular Sciences·Padideh KarimiMarius Ader
Jan 31, 2019·International Journal of Molecular Sciences·Thierry Léveillard, Laurence Klipfel
May 15, 2019·Biology·Janis T Eells
May 20, 2020·Frontiers in Cell and Developmental Biology·Raju V S Rajala
May 27, 2020·Oxidative Medicine and Cellular Longevity·Ravirajsinh N JadejaPamela M Martin
Oct 14, 2020·Investigative Ophthalmology & Visual Science·Jin Kyun OhStephen H Tsang
Jan 26, 2021·JCI Insight·David M WuConstance L Cepko
Dec 4, 2020·International Journal of Molecular Sciences·Janusz BlasiakKai Kaarniranta
Feb 3, 2021·International Journal of Molecular Sciences·Yue RuanAdrian Gericke
Jan 11, 2021·Progress in Retinal and Eye Research·Daniel T Hass, Colin J Barnstable
Feb 28, 2020·Progress in Retinal and Eye Research·Aparna LakkarajuDavid S Williams
Apr 17, 2020·Progress in Retinal and Eye Research·Kai KaarnirantaDeborah Ferrington
Mar 23, 2021·Cellular and Molecular Life Sciences : CMLS·Angela ArmentoSimon J Clark
May 5, 2021·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·Craig BeesonBärbel Rohrer
May 8, 2021·Nature Reviews. Disease Primers·Monika FleckensteinEmily Y Chew
May 9, 2021·The British Journal of Ophthalmology·Rasha A AlshaikhChristian Waeber
May 11, 2021·Critical Reviews in Food Science and Nutrition·Kristin KruegerMarietta Zille
Jun 3, 2021·International Journal of Molecular Sciences·Anuradha DhingraKathleen Boesze-Battaglia

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Methods Mentioned

BETA
electrophoresis
PCR

Software Mentioned

OxPhos
Tufm

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