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Recombinant Membrane-targeted Form of CD59 Inhibits the Growth of Choroidal Neovascular Complex in Mice

Bora, N. S., Jha, P., Lyzogubov, V. V., Kaliappan, S., Liu, J., Tytarenko, R. G., Fraser, Deborah A., Morgan, Bryan Paul and Bora, P. S. 2010. Recombinant Membrane-targeted Form of CD59 Inhibits the Growth of Choroidal Neovascular Complex in Mice. Journal of Biological Chemistry 285 (44) , pp. 33826-33833. 10.1074/jbc.M110.153130

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: Q Science > Q Science (General)
R Medicine > R Medicine (General)
Uncontrolled Keywords: Apoptosis; Complement; Eye; Immunology; Inflammation; CD59 Age-related Macular Degeneration; Choroidal Neovascularization; Complement Regulatory Proteins; Membrane Attack Complex
Publisher: American Society for Biochemistry and Molecular Biology
ISSN: 0021-9258
Last Modified: 04 Jun 2017 03:43

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