Purchase this article with an account.
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.
Download citation file:
© 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.
This PDF is available to Subscribers Only