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Should I Stay or Should I Go? Trafficking of Sub-Lytic MAC in the Retinal Pigment Epithelium

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Book cover Retinal Degenerative Diseases

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 801))

Abstract

Assembly of sub-lytic C5b-9 membrane attack complexes (MAC) on the plasma membrane of retinal pigment epithelial cells contributes to the pathogenesis of age-related macular degeneration. C5b-9 pores induce calcium influx, which activates signaling pathways that compromise cell function. Mechanisms that limit sub-lytic MAC activity include: cell surface complement regulatory proteins CD46, CD55, and CD59 that inhibit specific steps of MAC formation; elimination of assembled MAC by exocytosis of membrane vesicles or by endocytosis and subsequent lysosomal degradation; and rapid resealing of pores by the exocytosis of lysosomes. Aging in the post-mitotic retinal pigment epithelium is characterized by the accumulation of cellular debris called lipofuscin, which has also been associated with retinal diseases such as age-related macular degeneration. Lipofuscin has been shown to activate complement components both in vitro and in vivo, suggesting that it could contribute complement-mediated dysfunction in the retinal pigment epithelium. Here, we discuss emerging evidence that vesicular trafficking in the retinal pigment epithelium is critical for efficient removal of MAC from the cell surface and for limiting inflammation in the outer retina.

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Abbreviations

AMD:

Age-related macular degeneration

ESCRT:

Endosomal sorting complexes required for transport

GPI:

Glycosylphosphatidylinositol

MAC:

Membrane attack complex

RPE:

Retinal pigment epithelium

SNARE:

Soluble N-ethylmaleimide sensitive factor Attachment protein Receptor

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Acknowledgments

The work was supported by the American Health Assistance Foundation (M2009093), Carl Marshall and Mildred Almen Reeves Foundation, Karl Kirchgessner Foundation, Research to Prevent Blindness Career Development Award, and Retina Research Foundation Rebecca Meyer Brown Professorship.

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Authors and Affiliations

  1. Department of Ophthalmology and Visual Sciences, School of Medicine and Public Health, University of Wisconsin-Madison, 1300 University Ave, MSC 3385, 53706, Madison, WI, USA

    Aparna Lakkaraju, Kimberly A. Toops & Jin Xu

  2. McPherson Eye Research Institute, University of Wisconsin-Madison, 1300 University Ave, MSC 3385, 53706, Madison, WI, USA

    Aparna Lakkaraju & Kimberly A. Toops

Authors
  1. Aparna Lakkaraju
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  2. Kimberly A. Toops
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  3. Jin Xu
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Corresponding author

Correspondence to Aparna Lakkaraju .

Editor information

Editors and Affiliations

  1. Department of Ophthalmology, University of Florida, Gainesville, Florida, USA

    John D. Ash

  2. University Hospital Zurich, Zurich, Switzerland

    Christian Grimm

  3. Cole Eye Institute at the Cleveland Clin Division of Ophthalmology, Cleveland, Ohio, USA

    Joe G. Hollyfield

  4. Dean A. McGee Eye Inst., University of Oklahoma Health Science Center, Oklahoma City, Oklahoma, USA

    Robert E. Anderson

  5. Beckman Vision Center, University of California, San Francisco School of Medicine, San Francisco, California, USA

    Matthew M. LaVail

  6. Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina, USA

    Catherine Bowes Rickman

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Lakkaraju, A., Toops, K., Xu, J. (2014). Should I Stay or Should I Go? Trafficking of Sub-Lytic MAC in the Retinal Pigment Epithelium. In: Ash, J., Grimm, C., Hollyfield, J., Anderson, R., LaVail, M., Bowes Rickman, C. (eds) Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology, vol 801. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3209-8_34

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  • DOI: https://doi.org/10.1007/978-1-4614-3209-8_34

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  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4614-3208-1

  • Online ISBN: 978-1-4614-3209-8

  • eBook Packages: MedicineMedicine (R0)

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