September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
SEMAPHORIN-3E RESISTANT TO CLEAVAGE BY FURINS INHIBITS CHOROIDAL NEOVASCULARIZATION
Author Affiliations & Notes
  • Agustina C Palacio
    Ophthalmology, University of Louisville, Louisville, Kentucky, United States
  • Shira Toledano
    Cancer Research and vascular Biology Center,The Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel
  • Huayi Lu
    Ophthalmology, University of Louisville, Louisville, Kentucky, United States
  • Ofra Kessler
    Cancer Research and vascular Biology Center,The Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel
  • Yoreh Barak
    Department of Ophthalmology, Rambam Medical Center, Haifa, Israel
  • Gera Neufeld
    Cancer Research and vascular Biology Center,The Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel
  • Shlomit Schaal
    Ophthalmology, University of Louisville, Louisville, Kentucky, United States
  • Footnotes
    Commercial Relationships   Agustina Palacio, None; Shira Toledano, None; Huayi Lu, None; Ofra Kessler, None; Yoreh Barak, None; Gera Neufeld, None; Shlomit Schaal, None
  • Footnotes
    Support  This project is supported by the Binational Science Foundation (Schaal, Barak 2015), by an unrestricted institutional grant from Research to Prevent Blindness (RPB), and by a grant from the Israel Science Foundation (Neufeld).
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 4421. doi:
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    • Get Citation

      Agustina C Palacio, Shira Toledano, Huayi Lu, Ofra Kessler, Yoreh Barak, Gera Neufeld, Shlomit Schaal; SEMAPHORIN-3E RESISTANT TO CLEAVAGE BY FURINS INHIBITS CHOROIDAL NEOVASCULARIZATION. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4421.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : The exudative form of age-related macular degeneration (AMD) results in choroidal neovascularization (CNV). Anti-VEGF agents are widely used to treat AMD, however the high rate of non-responders calls for the exploration of anti-angiogenic agents that act independently from the VEGF pathway. This study was designed to investigate whether a point mutated form of the anti-angiogenic semaphorin-3E which was rendered resistant to cleavage by furin like pro-protein convertases (UNCL Sema3E) can be used to effectively inhibit laser induced CNV formation in a rat and a mouse model.

Methods : CNV was induced in the eyes of Evans-Long rats (n=16) and also in the eyes of C57B mice (n=20) by laser photocoagulation followed by an intravitreal injection of either 50 µg or 5 µg for the rat and the mice model respectively UNCL-Sema3E, 50 µg Avastin® (bevacizumab), 5 µg EYLEA® (aflibercept) or vehicle as control. After a week flat whole mounts of retinas where used to determine CNV frequency and size. Results were assessed by the staining of blood vessels with isolectin or with dextran green and calculating the area of stained blood vessels using the Image-J morphometric software. Visual function was assessed using a non-invasive OptoMotry © optokinetic testing system.

Results : UNCL-Sema3E (50 µg) injected into the vitreous cavity of rats reduced the area of laser induced CNV by 50% (64040 ± 7321 μm2 for controls (n=61) vs 32720 ±- 2369 μm2 (n=65), P<0.001) displaying efficacy similar to that of bevacizumab (32062±- 1806μm2 (n=54), P<0.001). UNCL-Sema3E (5µg) injected into the vitreous cavity of mice reduced the area of laser induced CNV by 35% (121063± 16957μm2 for controls (n=48) vs 78400± 8802μm2 (n=64), P<0.05) displaying somewhat lower efficacy than that of EYLEA (48713± 7255 μm2 (n=40), P<0.0001).

Conclusions : UNCL-Sema3E significantly inhibits laser induced CNV formation with similar efficiently as bevacizumab, but less efficiently than EYLEA. UNCL-Sema3E did not compromise visual acuity in optokinetic assays. UNCL-Sema3E mechanism of action differs from current therapies that block VEGF, therefore, UNCL-Sema3E carries the promise to become an adjunct therapeutic agent for the treatment of exudative AMD that is refractory to current treatments.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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