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Retinal Degenerative Diseases pp 213–219Cite as

The Role of Complement Dysregulation in AMD Mouse Models

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

Abstract

Variations in several complement genes are now known to be significant risk factors for the development of age-related macular degeneration (AMD). Despite dramatic effects on disease susceptibility, the underlying mechanisms by which common polymorphisms in complement proteins alter disease risk have remained unclear. Genetically modified mice in which the activity of the complement has been altered are available and can be used to investigate the role of complement in the pathogenesis of AMD. In this mini review, we will discuss some existing complement models of AMD and our efforts to develop and characterize the ocular phenotype in a variety of mice in which complement is either chronically activated or inhibited. A spectrum of complement dysregulation was modeled on the APOE4 AMD mouse model by crossing these mice to complement factor H knockout (cfh−/−) mice to test the impact of excess complement activation, and by crossing them to soluble-complement-receptor-1-related protein y (sCrry) mice, in which sCrry acts as a potent inhibitor of mouse complement acting in a manner similar to CFH. In addition, we have also generated humanized CFH mice expressing normal and risk variants of CFH.

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Acknowledgments

sCrry and cfh−/− mice were kindly provided by Drs. R. J. Quigg (University of Chicago, IL) and M. Botto (Imperial College, London), respectively. The work of the authors is supported by NIH Grants EY019038, P30 EY005722, an Edward N. & Della L. Thome Memorial Foundation Award, and Research to Prevent Blindness, Inc. Medical Student Fellowship awards to JGC and WZ.

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Authors and Affiliations

  1. Department of Ophthalmology, Duke University Medical Center, 2351 Erwin Rd, 27710, Durham, NC, USA

    Jin-Dong Ding, Una Kelly, Marybeth Groelle, Joseph G. Christenbury, Wenlan Zhang & Catherine Bowes Rickman

  2. Departments of Ophthalmology and Cell Biology, Duke University Medical Center, 2351 Erwin Rd, 27710, Durham, NC, USA

    Catherine Bowes Rickman

  3. Duke Eye Center, Duke University Medical Center, AERI Rm 5010, Post Box 3802, 27710, Durham, NC, USA

    Catherine Bowes Rickman

Authors
  1. Jin-Dong Ding
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  2. Una Kelly
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  3. Marybeth Groelle
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  4. Joseph G. Christenbury
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  5. Wenlan Zhang
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  6. Catherine Bowes Rickman
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Corresponding author

Correspondence to Catherine Bowes Rickman .

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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Ding, JD., Kelly, U., Groelle, M., Christenbury, J., Zhang, W., Bowes Rickman, C. (2014). The Role of Complement Dysregulation in AMD Mouse Models. 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_28

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  • DOI: https://doi.org/10.1007/978-1-4614-3209-8_28

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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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