July 2018
Volume 59, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2018
Classical pathway complement activation contributes to photoreceptor degeneration
Author Affiliations & Notes
  • Kenneth J Katschke
    Immunology, Genentech, South San Francisco, California, United States
  • Hongkang Xi
    Immunology, Genentech, South San Francisco, California, United States
  • Christian Cox
    Immunology, Genentech, South San Francisco, California, United States
  • Tom Truong
    Immunology, Genentech, South San Francisco, California, United States
  • Yann Malato
    Immunology, Genentech, South San Francisco, California, United States
  • Justin Elstrott
    Neuroscience, Genentech, South San Francisco, California, United States
  • Jianhua Tao
    Pathology, Genentech, South San Francisco, California, United States
  • Lauri Diehl
    Pathology, Genentech, South San Francisco, California, United States
  • Menno Van Lookeren Campagne
    Immunology, Genentech, South San Francisco, California, United States
  • Footnotes
    Commercial Relationships   Kenneth Katschke, Genentech (E); Hongkang Xi, Genentech (E); Christian Cox, Genentech (E); Tom Truong, Genentech (E); Yann Malato, Genentech (E); Justin Elstrott, Genentech (E); Jianhua Tao, Genentech (E); Lauri Diehl, Genentech (E); Menno Van Lookeren Campagne, Genentech (E)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 5563. doi:
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    • Get Citation

      Kenneth J Katschke, Hongkang Xi, Christian Cox, Tom Truong, Yann Malato, Justin Elstrott, Jianhua Tao, Lauri Diehl, Menno Van Lookeren Campagne; Classical pathway complement activation contributes to photoreceptor degeneration. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5563.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Polymorphisms in complement genes have been linked to age-related macular degeneration (AMD). We sought to further understand how classical complement activation contributes to photoreceptor loss using human donor eyes and a murine model of retinal degeneration.

Methods : Human eye samples from AMD and control patients were collected and stained for C4 deposition. Wildtype (C4+/+) and C4-deficient (C4-/-) mice were treated with sodium iodate (NaIO3) to induce retinal degeneration. Retina cell loss was measured in vivo by SD-OCT (Heidelberg) and ex vivo by flow cytometry and morphometry on H&E sections. Photoreceptor function was measured using electroretinogram (ERG) recordings.

Results : C4 deposition on photoreceptor outer segments was detected in 12 out of 18 AMD donor eyes and in 1 out of 13 control donor eyes. C4-/- mice showed a 63% reduction of recruited macrophages as compared to C4+/+ mice 3 days following NaIO3 treatment. Retinas of C4-/- mice were protected from NaIO3-induced photoreceptor degeneration as demonstrated by 26% thicker retinas and 42% more photoreceptors compared to C4+/+ mice, 7 days following NaIO3. By morphometry peripheral photoreceptor outer segment length was increased 5.3-fold in C4-/- compared to C4+/+. ERG a wave amplitudes, but not b wave amplitudes, were improved 1.6-fold in C4-/- vs. C4+/+ mice.

Conclusions : In post-mortem eyes, C4 was activated on photoreceptor outer segments of donors with AMD. Activation of the classical/lectin complement pathway contributed to retinal degeneration secondary to NaIO3-induced RPE loss by increasing macrophage recruitment associated with progressive loss of photoreceptor function. Combined, these results suggest that classical pathway complement activation may contribute to photoreceptor loss in AMD.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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