Cited by 53Retinal Diseases and TreatmentsComplement system in diseasesAngiogenesis and VEGF in Cancer

Recombinant membrane-targeted form of CD59 inhibits the growth of choroidal neovascular complex in mice

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Bora, Nalini S., Jha, Purushottam, Lyzogubov, Valeriy V., Kaliappan, Sankaranarayanan, Liu, Juan, Tytarenko, Ruslana G., Fraser, Deborah A., Morgan, B. Paul +1 more·2010·Journal of Biological Chemistry

Abstract

This study was designed to explore the effect of recombinant, membrane-targeted CD59 (rCD59-APT542) on the growth and size of fully developed neovascular complex using the murine model of laser-induced choroidal neovascularization (CNV). CNV was induced by laser photocoagulation in C57BL/6 mice using an argon laser, and the animals received rCD59-APT542 via intravitreal (ivt) route. Western blot analysis, immunohistochemistry, and total complement hemolytic assay demonstrated that exogenously administered rCD59-APT542 was incorporated as well as retained in RPE and choroid and was functionally active in vivo. Single ivt injection during the growth of the CNV (i.e. at day 3 post-laser) resulted in ∼79% inhibition of the further growth of neovascular complex. The size of the CNV complex was significantly (p < 0.05) reduced by the administration of rCD59-APT542 after the CNV complex has fully developed (i.e. at day 7 post-laser). Treatment with rCD59-APT542 blocked the formation of membrane attack complex (MAC), increased apoptosis and decreased cell proliferation in the neovascular complex. On the basis of results presented here we conclude that recombinant membrane targeted CD59 inhibited the growth of the CNV complex and reduced the size of fully developed CNV in the laser-induced mouse model. We propose that a combination of two mechanisms: increased apoptosis and decreased cell proliferation, both resulting from local inhibition of MAC, may be responsible for inhibition of CNV by rCD59-APT542.

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Crossref · 10.1074/jbc.m110.153130

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  • Several experiments using mouse models of laser-induced CNV have demonstrated that all complement pathways, particularly the alternative and terminal pathways, play a significant role in angiogenesis.

    “Several experiments using mouse models of laser-induced CNV have demonstrated that all complement pathways, particularly the alternative and terminal pathways, play a significant role in angiogenesis [150,152,153,154,155,156,157,158,159,160,161,162,163].”

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Research works printed but not linked: 2

  1. Ryan, S. J. (1979) Trans. Am. Ophthalmol. Soc. 77, 707-745
  2. Acosta, J., Hettinga, J., Flu ¨ckiger, R., Krumrei, N., Goldfine, A., Angarita, L., and Halperin, J. (2000) Proc. Natl. Acad. Sci. U.S.A. 97, 5450 -5455

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Authors
Bora, N. S., Jha, P., Lyzogubov, V. V., Kaliappan, S., Liu, J., Tytarenko, R. G., Fraser, D. A., Morgan, B. P., & Bora, P. S.
Affiliations
  • University of Arkansas for Medical Sciences (US)
  • Cardiff University (GB)
Corresponding author
  • Bora, Nalini S.
  • Bora, Puran S.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2010-10
Volume
285
Issue
44
Pages
33826-33833
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2084557754
Cited by
53
References
29
Citations by year
2025: 1 · 2024: 4 · 2023: 3 · 2022: 1 · 2021: 3 · 2020: 2 · 2019: 1 · 2018: 3 · 2017: 2 · 2016: 7 · 2015: 2 · 2014: 8 · 2013: 1 · 2012: 8
FWCI
5.58
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • University of Arkansas for Medical Sciences
  • National Institutes of Health (2P20 RR16460)
  • National Eye Institute (R01EY014623, EY 014623, R01EY018812, EY018812)
  • National Center for Research Resources (2 P20 RR-16460, P20RR016460, S10RR019395, 1 S10 RR 19395)
Topics
  • Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
  • Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
Keywords
CD59, choroidal neovascularization, membrane attack complex, complement inhibition, laser-induced CNV, retinal pigment epithelium, choroid, apoptosis, cell proliferation, intravitreal injection, age-related macular degeneration
MeSH terms
Animals, Cell Membrane, Complement System Proteins, Immunohistochemistry, Inflammation, Macular Degeneration, Male, Mice, Inbred C57BL, Neovascularization, Pathologic, Recombinant Proteins, Apoptosis, CD59 Antigens, Choroidal Neovascularization, Cell Proliferation, Mice

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