June 2020
Volume 61, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2020
Proteomic analysis of vitreous humor samples obtained from donors with and without age-related macular degeneration (AMD) reveal an overactivation of complement protein expression.
Author Affiliations & Notes
  • Anna Buchberger
    Research and Preclinical, Gyroscope Therapeutics, London, United Kingdom
  • James Francis
    Research and Preclinical, Gyroscope Therapeutics, London, United Kingdom
  • Ashley Frazer-Abel
    Exsera BioLabs, Aurora, Colorado, United States
  • Selina McHarg
    Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom
  • Paul N Bishop
    Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom
  • Scott Ellis
    Research and Preclinical, Gyroscope Therapeutics, London, United Kingdom
  • Jane Hughes
    Research and Preclinical, Gyroscope Therapeutics, London, United Kingdom
  • Footnotes
    Commercial Relationships   Anna Buchberger, Gyroscope Therapeutics (E); James Francis, Gyroscope Therapeutics (E); Ashley Frazer-Abel, Exsera BioLabs (E); Selina McHarg, None; Paul Bishop, None; Scott Ellis, Gyroscope Therapeutics (E); Jane Hughes, Gyroscope Therapeutics (E)
  • Footnotes
    Support  The Macular Society
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 3650. doi:
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      Anna Buchberger, James Francis, Ashley Frazer-Abel, Selina McHarg, Paul N Bishop, Scott Ellis, Jane Hughes; Proteomic analysis of vitreous humor samples obtained from donors with and without age-related macular degeneration (AMD) reveal an overactivation of complement protein expression.. Invest. Ophthalmol. Vis. Sci. 2020;61(7):3650.

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

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Abstract

Purpose : AMD is considered a chronic inflammatory disease which can be associated with defective and insufficient regulation of the alternative complement pathway. This study aimed to evaluate levels of complement proteins from human vitreous isolated from eyes of donors diagnosed with early AMD, neovascular AMD and geographic atrophy (GA), compared to healthy eyes.

Methods : Vitreous humor, obtained from Manchester Eye Tissue Repository, was harvested from post-mortem eyes with no macular changes (n=10) or macroscopic changes compatible with diagnoses of early AMD (n=11), neovascular AMD (n=6) and geographic atrophy (n=6). Complement proteins from the classical, lectin and alternative complement pathways were analysed by means of enzyme-linked immunosorbent assays or multiplex assays.

Results : A significant reduction in levels of C5 was noted in all AMD types ((mean±SD); healthy = 542±256 ng/mL; all AMD = 97±199 ng/mL; p<0.001). C5a levels did not differ between groups. The ratio of C3 to C3a was significantly decreased in vitreous humor isolated from early and GA donors compared to health eyes (healthy = 5828±3462; early AMD = 2466±1661; dry AMD = 1146±727; p<0.05). No differences in levels of classical or MBL pathway complement proteins (C1q, C2, C4, MBL) were detected. Additionally, there were no differences in complement regulatory proteins (Factors I, H, B and D or properdin) between groups.

Conclusions : This study reveals a decrease in C5 levels and/or the C3/C3a ratio which suggests that the complement system is overactivated at early stages of AMD through to later stages of disease. Whilst no differences in regulatory complement proteins were observed between groups, supplementation of these regulatory proteins may offer a therapeutic strategy for AMD patients.

This is a 2020 ARVO Annual Meeting abstract.

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