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HGF and VEGF-A and Their Receptors Show Expression and Angiogenic Effects on Human Choroidal Endothelial Cells: Implications for Treatments of Neovascular Age-Related Macular Degeneration

Academic Ophthalmology, Division of Clinical Neuroscience, University of Nottingham, B Floor, Eye and ENT Building, Queen’s Medical Centre, Nottingham NG7 2UH, UK
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Academic Editor: Pier Paolo Claudio
Int. J. Transl. Med. 2021, 1(1), 69-82; https://0-doi-org.brum.beds.ac.uk/10.3390/ijtm1010006
Received: 26 March 2021 / Revised: 6 May 2021 / Accepted: 25 May 2021 / Published: 16 June 2021
Intraocular neovascularisation is associated with common blinding conditions including neovascular age-related macular degeneration (nAMD). Vascular endothelial growth factor (VEGF) is central in driving choroidal neovascularisation in this disease. Many clinical therapies target VEGF-A with intravitreal anti-VEGF drugs, which, however, have limited efficacy and require repeated, prolonged treatment. Other cytokines are known to be involved, including hepatocyte growth factor (HGF), which is shown to have a role in the early stages of nAMD. We investigated the effect of HGF and its co-operation with VEGF-A on human choroidal endothelial cells (CEC). The expression of HGF and related molecules in CEC was investigated using immunofluorescence, Western blotting and flow cytometry. In vitro assays for proliferation, tubule formation and migration were used to assess the potential role of HGF in neovascularisation. Primary human CEC expressed HGF, VEGF-A and their receptors MET and VEGF receptor 2 (VEGFR2). HGF increased CEC proliferation, tubule formation and migration; the increased proliferation and migration appeared to be additive with that achieved with VEGF-A. This study provides insight into growth factor co-operation in CEC signalling and indicates that simultaneous blockage of multiple growth factors or common downstream signalling pathways may provide a more sustained treatment response, enhancing treatments in nAMD. View Full-Text
Keywords: hepatocyte growth factor (HGF); vascular endothelial growth factor (VEGF); age-related macular degeneration; neovascularisation; choroid; cytokine co-operation hepatocyte growth factor (HGF); vascular endothelial growth factor (VEGF); age-related macular degeneration; neovascularisation; choroid; cytokine co-operation
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MDPI and ACS Style

Stewart, E.A.; Allen, C.L.; Samaranayake, G.J.; Stubington, T.; Akhtar, R.; Branch, M.J.; Amoaku, W.M. HGF and VEGF-A and Their Receptors Show Expression and Angiogenic Effects on Human Choroidal Endothelial Cells: Implications for Treatments of Neovascular Age-Related Macular Degeneration. Int. J. Transl. Med. 2021, 1, 69-82. https://0-doi-org.brum.beds.ac.uk/10.3390/ijtm1010006

AMA Style

Stewart EA, Allen CL, Samaranayake GJ, Stubington T, Akhtar R, Branch MJ, Amoaku WM. HGF and VEGF-A and Their Receptors Show Expression and Angiogenic Effects on Human Choroidal Endothelial Cells: Implications for Treatments of Neovascular Age-Related Macular Degeneration. International Journal of Translational Medicine. 2021; 1(1):69-82. https://0-doi-org.brum.beds.ac.uk/10.3390/ijtm1010006

Chicago/Turabian Style

Stewart, Elizabeth A., Claire L. Allen, Govindi J. Samaranayake, Thomas Stubington, Rukhsar Akhtar, Matthew J. Branch, and Winfried M. Amoaku 2021. "HGF and VEGF-A and Their Receptors Show Expression and Angiogenic Effects on Human Choroidal Endothelial Cells: Implications for Treatments of Neovascular Age-Related Macular Degeneration" International Journal of Translational Medicine 1, no. 1: 69-82. https://0-doi-org.brum.beds.ac.uk/10.3390/ijtm1010006

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