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Mitochondria: The Retina’s Achilles’ Heel in AMD

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Book cover Age-related Macular Degeneration

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1256))

Abstract

Strong experimental evidence from studies in human donor retinas and animal models supports the idea that the retinal pathology associated with age-related macular degeneration (AMD) involves mitochondrial dysfunction and consequent altered retinal metabolism. This chapter provides a brief overview of mitochondrial structure and function, summarizes evidence for mitochondrial defects in AMD, and highlights the potential ramifications of these defects on retinal health and function. Discussion of mitochondrial haplogroups and their association with AMD brings to light how mitochondrial genetics can influence disease outcome. As one of the most metabolically active tissues in the human body, there is strong evidence that disruption in key metabolic pathways contributes to AMD pathology. The section on retinal metabolism reviews cell-specific metabolic differences and how the metabolic interdependence of each retinal cell type creates a unique ecosystem that is disrupted in the diseased retina. The final discussion includes strategies for therapeutic interventions that target key mitochondrial pathways as a treatment for AMD.

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Acknowledgements

This work was supported by grants from the National Institutes of Health / National Eye Institute (R01 EY026012 and R01 EY028554 to DAF; R01EY0127363 to MCK, R01 EY06641 and R01 EY017863 to JBH, R01EY016459-11 and R01EY031720 to JDA), the Elaine and Robert Larson Endowed Vision Research Chair, an anonymous benefactor for AMD research, the Lindsay Family Foundation (to DAF); the Discovery Eye Foundation, Polly and Michael Smith, Iris and B. Gerald Cantor Foundation (to MCK), and an unrestricted grant from Research to Prevent Blindness to the Department of Ophthalmology, University of Florida and to the Gavin Herbert Eye Institution, University of California.

The authors wish to acknowledge the insightful discussions at the meetings of the “Ryan’s Initiative for Macular Research” as the basis for the collaborative writing of this chapter.

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Authors and Affiliations

  1. Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, MN, USA

    Deborah A. Ferrington

  2. Gavin Herbert Eye Institute, University of California, Irvine, Irvine, CA, USA

    M. Cristina Kenney & Shari R. Atilano

  3. Departments of Biochemistry and Ophthalmology, University of Washington, Seattle, WA, USA

    James B. Hurley

  4. Department of Ophthalmology, University of Florida, Gainesville, FL, USA

    Emily E. Brown & John D. Ash

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  1. Deborah A. Ferrington
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  5. Emily E. Brown
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  6. John D. Ash
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Correspondence to Deborah A. Ferrington .

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  1. Division of Epidemiology and Clinical Applications, National Eye Institute, National Institutes of Health, Bethesda, MD, USA

    Emily Y. Chew

  2. Neurobiology-Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD, USA

    Anand Swaroop

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Ferrington, D.A., Kenney, M.C., Atilano, S.R., Hurley, J.B., Brown, E.E., Ash, J.D. (2021). Mitochondria: The Retina’s Achilles’ Heel in AMD. In: Chew, E.Y., Swaroop, A. (eds) Age-related Macular Degeneration. Advances in Experimental Medicine and Biology, vol 1256. Springer, Cham. https://doi.org/10.1007/978-3-030-66014-7_10

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