Inhibition of Ocular Neovascularization by Co-Inhibition of VEGF-A and PLGF
Background/Aims: Age-related macular degeneration (AMD) appears to be a disease with increasing incidence in Western countries and may develop into acquired blindness. Choroidal neovascularization (CNV) is the most frequent cause for AMD, and is commonly induced by regional inflammation. Past studie...
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| Format: | Article |
| Language: | English |
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Cell Physiol Biochem Press GmbH & Co KG
2015-03-01
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| Series: | Cellular Physiology and Biochemistry |
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| Online Access: | http://www.karger.com/Article/FullText/373990 |
| _version_ | 1818232938338189312 |
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| author | Xiaochuan Huo Youxiang Li Yuhua Jiang Xiaoyun Sun Lixue Gu Wenshi Guo Dapeng Sun |
| author_facet | Xiaochuan Huo Youxiang Li Yuhua Jiang Xiaoyun Sun Lixue Gu Wenshi Guo Dapeng Sun |
| author_sort | Xiaochuan Huo |
| collection | DOAJ |
| description | Background/Aims: Age-related macular degeneration (AMD) appears to be a disease with increasing incidence in Western countries and may develop into acquired blindness. Choroidal neovascularization (CNV) is the most frequent cause for AMD, and is commonly induced by regional inflammation. Past studies have highlighted vascular endothelial growth factor A (VEGF-A) as a major trigger for CNV. However, studies on the associated angiogenic factors other than VEGF-A are lacking. Methods: Here, we used a well-established laser burn (LB)-induced experimental CNV mouse model to study the molecular mechanisms underlying the development of CNV after ocular injury. We analyzed vessel density by lectin labeling. We isolated macrophages, endothelial cells and other cell types by flow cytometry, and analyzed levels of different angiogenic factors in these populations. We used antisera against VEGF-A (aVEGF) and/or antisera against placental growth factor (PLGF; aPLGF) to antagonize CNV. We used an antibody-driven toxin to selectively eliminate macrophages to evaluate the role of macrophages in CNV. We also examined expression of PLGF in macrophage subtypes. Results: The choroidal vessel density increased significantly 7 days after LB. LB increased significantly the levels of VEGF-A and PLGF in mouse eyes. Treatment with aVEGF significantly blunted increases in vessel density by LB. Treatment with aPLGF alone did not significantly reduce increases in vessel density. However, aPLGF significantly increased the inhibitory effects of aVEGF on vessel density increases. While VEGF-A was produced by endothelial cells, macrophages and other types at similar levels, PLGF seemed to be predominantly produced by macrophages. Selective macrophage depletion significantly reduced CNV. M2, but M1 macrophages produced high levels of PLGF. Conclusions: Together, our data suggest a previously unappreciated role of PLGF in coordination with VEGF-A to regulate CNV during ocular injury. Our study highlights macrophages and their production of PLGF as novel targets for CNV therapy. |
| first_indexed | 2024-12-12T11:14:14Z |
| format | Article |
| id | doaj.art-d4810eaec3604afb946e43da1ff79545 |
| institution | Directory Open Access Journal |
| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-12-12T11:14:14Z |
| publishDate | 2015-03-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
| record_format | Article |
| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-d4810eaec3604afb946e43da1ff795452022-12-22T00:26:13ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782015-03-013551787179610.1159/000373990373990Inhibition of Ocular Neovascularization by Co-Inhibition of VEGF-A and PLGFXiaochuan HuoYouxiang LiYuhua JiangXiaoyun SunLixue GuWenshi GuoDapeng SunBackground/Aims: Age-related macular degeneration (AMD) appears to be a disease with increasing incidence in Western countries and may develop into acquired blindness. Choroidal neovascularization (CNV) is the most frequent cause for AMD, and is commonly induced by regional inflammation. Past studies have highlighted vascular endothelial growth factor A (VEGF-A) as a major trigger for CNV. However, studies on the associated angiogenic factors other than VEGF-A are lacking. Methods: Here, we used a well-established laser burn (LB)-induced experimental CNV mouse model to study the molecular mechanisms underlying the development of CNV after ocular injury. We analyzed vessel density by lectin labeling. We isolated macrophages, endothelial cells and other cell types by flow cytometry, and analyzed levels of different angiogenic factors in these populations. We used antisera against VEGF-A (aVEGF) and/or antisera against placental growth factor (PLGF; aPLGF) to antagonize CNV. We used an antibody-driven toxin to selectively eliminate macrophages to evaluate the role of macrophages in CNV. We also examined expression of PLGF in macrophage subtypes. Results: The choroidal vessel density increased significantly 7 days after LB. LB increased significantly the levels of VEGF-A and PLGF in mouse eyes. Treatment with aVEGF significantly blunted increases in vessel density by LB. Treatment with aPLGF alone did not significantly reduce increases in vessel density. However, aPLGF significantly increased the inhibitory effects of aVEGF on vessel density increases. While VEGF-A was produced by endothelial cells, macrophages and other types at similar levels, PLGF seemed to be predominantly produced by macrophages. Selective macrophage depletion significantly reduced CNV. M2, but M1 macrophages produced high levels of PLGF. Conclusions: Together, our data suggest a previously unappreciated role of PLGF in coordination with VEGF-A to regulate CNV during ocular injury. Our study highlights macrophages and their production of PLGF as novel targets for CNV therapy.http://www.karger.com/Article/FullText/373990Age-related macular degeneration (AMD)Choroidal neovascularization (CNV)Placental growth factor (PLGF)Vascular endothelial growth factor A (VEGF-A)Laser burn (LB)Macrophages |
| spellingShingle | Xiaochuan Huo Youxiang Li Yuhua Jiang Xiaoyun Sun Lixue Gu Wenshi Guo Dapeng Sun Inhibition of Ocular Neovascularization by Co-Inhibition of VEGF-A and PLGF Cellular Physiology and Biochemistry Age-related macular degeneration (AMD) Choroidal neovascularization (CNV) Placental growth factor (PLGF) Vascular endothelial growth factor A (VEGF-A) Laser burn (LB) Macrophages |
| title | Inhibition of Ocular Neovascularization by Co-Inhibition of VEGF-A and PLGF |
| title_full | Inhibition of Ocular Neovascularization by Co-Inhibition of VEGF-A and PLGF |
| title_fullStr | Inhibition of Ocular Neovascularization by Co-Inhibition of VEGF-A and PLGF |
| title_full_unstemmed | Inhibition of Ocular Neovascularization by Co-Inhibition of VEGF-A and PLGF |
| title_short | Inhibition of Ocular Neovascularization by Co-Inhibition of VEGF-A and PLGF |
| title_sort | inhibition of ocular neovascularization by co inhibition of vegf a and plgf |
| topic | Age-related macular degeneration (AMD) Choroidal neovascularization (CNV) Placental growth factor (PLGF) Vascular endothelial growth factor A (VEGF-A) Laser burn (LB) Macrophages |
| url | http://www.karger.com/Article/FullText/373990 |
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