Activated Protein C (APC) and 3K3A-APC-Induced Regression of Choroidal Neovascularization (CNV) Is Accompanied by Vascular Endothelial Growth Factor (VEGF) Reduction
The activated protein C (APC) ability to inhibit choroidal neovascularization (CNV) growth and leakage was recently shown in a murine model. A modified APC, 3K3A-APC, was designed to reduce anticoagulant activity while maintaining full cytoprotective properties, thus diminishing bleeding risk. We ai...
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| Format: | Article |
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MDPI AG
2021-02-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/11/3/358 |
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| author | Tami Livnat Yehonatan Weinberger José A. Fernández Alaa Bashir Gil Ben-David Dahlia Palevski Sarina Levy-Mendelovich Gili Kenet Ivan Budnik Yael Nisgav John H. Griffin Dov Weinberger |
| author_facet | Tami Livnat Yehonatan Weinberger José A. Fernández Alaa Bashir Gil Ben-David Dahlia Palevski Sarina Levy-Mendelovich Gili Kenet Ivan Budnik Yael Nisgav John H. Griffin Dov Weinberger |
| author_sort | Tami Livnat |
| collection | DOAJ |
| description | The activated protein C (APC) ability to inhibit choroidal neovascularization (CNV) growth and leakage was recently shown in a murine model. A modified APC, 3K3A-APC, was designed to reduce anticoagulant activity while maintaining full cytoprotective properties, thus diminishing bleeding risk. We aimed to study the ability of 3K3A-APC to induce regression of CNV and evaluate vascular endothelial growth factor (VEGF) role in APC’s activities in the retina. CNV was induced by laser photocoagulation on C57BL/6J mice. APC and 3K3A-APC were injected intravitreally after verification of CNV presence. CNV volume and vascular penetration were evaluated on retinal pigmented epithelium (RPE)-choroid flatmount by fluorescein isothiocyanate (FITC)-dextran imaging. VEGF levels were measured using immunofluorescence anti-VEGF staining. We found that 3K3A-APC induced regression of pre-existing CNV. VEGF levels, measured in the CNV lesion sites, significantly decreased upon APC and 3K3A-APC treatment. Reduction in VEGF was sustained 14 days post a single APC injection. As 3K3A-APC retained APCs’ activities, we conclude that the anticoagulant properties of APC are not mandatory for APC activities in the retina and that VEGF reduction may contribute to the protective effects of APC and 3K3A-APC. Our results highlight the potential use of 3K3A-APC as a novel treatment for CNV and other ocular pathologies. |
| first_indexed | 2024-03-09T00:29:08Z |
| format | Article |
| id | doaj.art-257408fbd8ea498eaece922f8cc88963 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-09T00:29:08Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-257408fbd8ea498eaece922f8cc889632023-12-11T18:37:12ZengMDPI AGBiomolecules2218-273X2021-02-0111335810.3390/biom11030358Activated Protein C (APC) and 3K3A-APC-Induced Regression of Choroidal Neovascularization (CNV) Is Accompanied by Vascular Endothelial Growth Factor (VEGF) ReductionTami Livnat0Yehonatan Weinberger1José A. Fernández2Alaa Bashir3Gil Ben-David4Dahlia Palevski5Sarina Levy-Mendelovich6Gili Kenet7Ivan Budnik8Yael Nisgav9John H. Griffin10Dov Weinberger11Rabin Medical Center, Ophthalmology Department and Laboratory of Eye Research Felsenstein Medical Research Center, Petah-Tikva 49100, IsraelRabin Medical Center, Ophthalmology Department and Laboratory of Eye Research Felsenstein Medical Research Center, Petah-Tikva 49100, IsraelDepartment of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USARabin Medical Center, Ophthalmology Department and Laboratory of Eye Research Felsenstein Medical Research Center, Petah-Tikva 49100, IsraelRabin Medical Center, Ophthalmology Department and Laboratory of Eye Research Felsenstein Medical Research Center, Petah-Tikva 49100, IsraelRabin Medical Center, Ophthalmology Department and Laboratory of Eye Research Felsenstein Medical Research Center, Petah-Tikva 49100, IsraelSackler Faculty of Medicine, Tel Aviv University, Tel-Aviv 69978, IsraelSackler Faculty of Medicine, Tel Aviv University, Tel-Aviv 69978, IsraelDepartment of Pathophysiology, Sechenov First Moscow State Medical University (Sechenov University), 119019 Moscow, RussiaRabin Medical Center, Ophthalmology Department and Laboratory of Eye Research Felsenstein Medical Research Center, Petah-Tikva 49100, IsraelDepartment of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USARabin Medical Center, Ophthalmology Department and Laboratory of Eye Research Felsenstein Medical Research Center, Petah-Tikva 49100, IsraelThe activated protein C (APC) ability to inhibit choroidal neovascularization (CNV) growth and leakage was recently shown in a murine model. A modified APC, 3K3A-APC, was designed to reduce anticoagulant activity while maintaining full cytoprotective properties, thus diminishing bleeding risk. We aimed to study the ability of 3K3A-APC to induce regression of CNV and evaluate vascular endothelial growth factor (VEGF) role in APC’s activities in the retina. CNV was induced by laser photocoagulation on C57BL/6J mice. APC and 3K3A-APC were injected intravitreally after verification of CNV presence. CNV volume and vascular penetration were evaluated on retinal pigmented epithelium (RPE)-choroid flatmount by fluorescein isothiocyanate (FITC)-dextran imaging. VEGF levels were measured using immunofluorescence anti-VEGF staining. We found that 3K3A-APC induced regression of pre-existing CNV. VEGF levels, measured in the CNV lesion sites, significantly decreased upon APC and 3K3A-APC treatment. Reduction in VEGF was sustained 14 days post a single APC injection. As 3K3A-APC retained APCs’ activities, we conclude that the anticoagulant properties of APC are not mandatory for APC activities in the retina and that VEGF reduction may contribute to the protective effects of APC and 3K3A-APC. Our results highlight the potential use of 3K3A-APC as a novel treatment for CNV and other ocular pathologies.https://www.mdpi.com/2218-273X/11/3/358activated protein C (APC)choroidal neovascularization (CNV)vascular endothelial growth factor (VEGF)Tie2retinamouse model |
| spellingShingle | Tami Livnat Yehonatan Weinberger José A. Fernández Alaa Bashir Gil Ben-David Dahlia Palevski Sarina Levy-Mendelovich Gili Kenet Ivan Budnik Yael Nisgav John H. Griffin Dov Weinberger Activated Protein C (APC) and 3K3A-APC-Induced Regression of Choroidal Neovascularization (CNV) Is Accompanied by Vascular Endothelial Growth Factor (VEGF) Reduction Biomolecules activated protein C (APC) choroidal neovascularization (CNV) vascular endothelial growth factor (VEGF) Tie2 retina mouse model |
| title | Activated Protein C (APC) and 3K3A-APC-Induced Regression of Choroidal Neovascularization (CNV) Is Accompanied by Vascular Endothelial Growth Factor (VEGF) Reduction |
| title_full | Activated Protein C (APC) and 3K3A-APC-Induced Regression of Choroidal Neovascularization (CNV) Is Accompanied by Vascular Endothelial Growth Factor (VEGF) Reduction |
| title_fullStr | Activated Protein C (APC) and 3K3A-APC-Induced Regression of Choroidal Neovascularization (CNV) Is Accompanied by Vascular Endothelial Growth Factor (VEGF) Reduction |
| title_full_unstemmed | Activated Protein C (APC) and 3K3A-APC-Induced Regression of Choroidal Neovascularization (CNV) Is Accompanied by Vascular Endothelial Growth Factor (VEGF) Reduction |
| title_short | Activated Protein C (APC) and 3K3A-APC-Induced Regression of Choroidal Neovascularization (CNV) Is Accompanied by Vascular Endothelial Growth Factor (VEGF) Reduction |
| title_sort | activated protein c apc and 3k3a apc induced regression of choroidal neovascularization cnv is accompanied by vascular endothelial growth factor vegf reduction |
| topic | activated protein C (APC) choroidal neovascularization (CNV) vascular endothelial growth factor (VEGF) Tie2 retina mouse model |
| url | https://www.mdpi.com/2218-273X/11/3/358 |
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