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Rafael Ufret-Vincenty, Bogale Aredo, Kaiyan Zhang, Cynthia X. Wang, Shusheng Wang, Jose Pulido, Philip E. Thorpe; Anti-phosphatidylserine Antibodies As A Potential New Therapy Against Choroidal Neovascularization. Invest. Ophthalmol. Vis. Sci. 2012;53(14):443.
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Despite the dramatic changes in clinical outcomes brought by anti-VEGF agents, additional drugs directed against different targets in the neovascular process are needed. This may allow for combination therapies that could potentially eradicate choroidal neovascularization (CNV). In normal cells the aminophospholipid phosphatidylserine (PS) is almost exclusively localized to the inner leaflet of the cell membrane’s lipid bilayer. Endothelial cells of tumor neovasculature lose their capacity to maintain PS asymmetry. Anti-PS antibodies bind to the newly exposed phosphatidylserine in the outer leaflet of the tumor vascular endothelium, mediating antibody-dependent cell-mediated cytotoxicity, and causing the collapse of the tumor neovasculature. Radiotherapy increases the exposure of PS in tumor vasculature, enhancing the antitumor effects of anti-PS antibodies. We propose to evaluate if there is also exposure of PS in CNV, and if anti-PS antibodies can treat CNV.
We induced CNV in B6 mice using the laser model. Immunostaining for PS was done after perfusing mice with an anti-PS antibody and paraffin-embedding the eyes. We tested the effect of intravitreal anti-PS antibodies alone, or in combination with eye radiation, on the CNV size as measured with ICAM-2 staining.
Paraffin sections of eyes perfused with an anti-PS antibody stained positive for PS. The staining co-localized with ICAM-2-stained CNV, demonstrating that PS was exposed on the choroidal neovascular membranes. The anti-PS antibody (11.31) led to a 52% reduction in the laser-induced CNV size (p=0.02) when injected intravitreally. We have established a system for irradiation of the eyes. We will show data on the effect of radiation alone or in combination with anti-PS antibodies on the neovascular complex.
Anti-phosphatidylserine antibodies may have therapeutic value in wet AMD alone or in combination with radiation or anti-VEGF agents.
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