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J. Liu, P. Jha, V. V. Lyzogubov, P. S. Bora, N. S. Bora; Recombinant Membrane-Targeted CD59 Inhibits the Growth of Choroidal Neovascular Complex in Murine Model of Laser-Induced Choroidal Neovascularization (CNV). Invest. Ophthalmol. Vis. Sci. 2010;51(13):405. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
This study was designed to explore the effect of recombinant, membrane targeted CD59 (rCD59-APT542) on the growth as well on the size of fully developed neo-vascular complex using the murine model of laser-induced choroidal neovascularization (CNV).
Argon laser photocoagulation was used to induce CNV in C57BL/6 mice. After laser treatment, animals received i.p. or subretinal injection of rCD59-APT542 at day 3 (during the growth of CNV) and sacrificed at day 7 post-laser. Another group of animals received i.p. (days 7 and 9 post-laser) or subretinal (day 7 post-laser) injection of rCD59-APT542 and sacrificed at day 12 post-laser (fully developed CNV). The presence of rCD59-APT542 in mouse RPE-choroid was analyzed using Western blot analysis. The incidence as well as the size of CNV complex was determined using flat mounted RPE-choroid-sclera, confocal microscopy and ImageJ program. MAC deposition in RPE-choroid was evaluated by immunohistochemistry.
Western blot analysis demonstrated that a single i.p. injection of rCD59-APT542 delivers the protein to the RPE-choroid and the protein is retained in these tissues for up to 5 days. MAC analysis revealed that exogenously administered rCD59-APT542 is functionally active in the RPE-choroid. Administration of rCD59-APT542 at day 3 post-laser resulted in ~ 74% (i.p. injection) and ~ 79% (subretinal injection) inhibition of the further growth of CNV complex compared to similar treatment with sterile PBS. Our results further demonstrated that treatment with rCD59-APT542 at days 7 and 9 post-laser also resulted in ~ 42% (i.p. injection) inhibition of the CNV complex in C57BL/6 mice compared to PBS injected control animals. A single subretinal injection of rCD59-APT542 at day 7 inhibited the CNV complex by ~ 44%.
Our results demonstrate that rCD59-APT542 inhibits the growth of CNV complex as well as the size of fully developed CNV in the laser-induced mouse model. We believe that membrane targeted CD59 may have therapeutic potential in humans since our present study mimics the frequent clinical presentation of AMD in humans.
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