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Endoplasmic Reticulum Stress as a Primary Pathogenic Mechanism Leading to Age-Related Macular Degeneration

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Retinal Degenerative Diseases

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 664))

Abstract

Age-related macular degeneration (AMD) is a multi-factorial disease and a leading cause of blindness. Proteomic and genetic data suggest that activation or de-repression of the alternate complement cascade of innate immunity is involved in end-stage disease. Several lines of evidence suggest that production of reactive oxygen species and chronic oxidative stress lead to protein and lipid modifications that initiate the complement cascade. Understanding the triggers of these pathogenic pathways and the site of the primary insult will be important for development of targeted therapeutics. Endoplasmic reticulum (ER) stress from misfolded mutant proteins and other sources are an important potential tributary mechanism. We propose that misfolded-protein-induced ER stress in the retinal-pigmented epithelium and/or choroid could lead to chronic oxidative stress, complement deregulation and AMD. Small molecules targeted to ER stress and oxidative stress could allow for a shift from disease treatment to disease prevention.

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Author information

Authors and Affiliations

  1. Departments of Ophthalmology and Biomedical Genetics, University of Rochester Eye Institute, University of Rochester Medical School, Rochester, NY, 14642, USA

    Richard T. Libby

  2. Departments of Ophthalmology and Anatomy and Institute for Human Genetics, University of California at San Francisco, San Francisco, CA, 94143, USA

    Douglas B. Gould

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  1. Richard T. Libby
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  2. Douglas B. Gould
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Correspondence to Douglas B. Gould .

Editor information

Editors and Affiliations

  1. Health Science Center, University of Oklahoma, Stanton L. Young Blvd. 608, Oklahoma City, 73104, USA

    Robert E. Anderson

  2. Division of Ophthalmology, Cleveland Clinic Foundation, Euclid Ave. 9500, Cleveland, 44195, USA

    Joe G. Hollyfield

  3. School of Medicine, University of California, San Francisco, Kirkham St. 10, San Francisco, 94143, USA

    Matthew M. LaVail

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Libby, R.T., Gould, D.B. (2010). Endoplasmic Reticulum Stress as a Primary Pathogenic Mechanism Leading to Age-Related Macular Degeneration. In: Anderson, R., Hollyfield, J., LaVail, M. (eds) Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology, vol 664. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-1399-9_46

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