Hepatocyte growth factor in neovascular age related macular degeneration: In vitro study of its effects on choroidal endothelial cells

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Abstract

Purpose

Intraocular angiogenesis is associated with a number of common blinding conditions including neovascular age-related macular degeneration (nAMD). The growth factor vascular endothelial growth factor (VEGF) is reported as being central in driving choroidal neovascularisation in nAMD. Many clinical nAMD therapies target VEGF with anti-VEGF drugs such as ranibizumab, bevacizumab and Aflibercept. These however have limited efficacy and require repeated, prolonged treatment. Other cytokines are known to be involved in nAMD including hepatocyte growth factor (HGF) which has been shown to have a role in the early stages of nAMD. Our aim was to elucidate the effect of HGF and its cooperation with VEGF on human choroidal endothelial cells (CEC).

Methods

The expression of HGF and related molecules in CEC was investigated using western blotting and flow cytometry. In vitro assays for proliferation, tubule formation and transendothelial permeability were used to assess the role of HGF in nAMD.

Results

Expression of HGF, VEGF and their receptors c-met and VEGFR2 and co-receptor CD44v6 was found in primary human CEC. Stimulation with HGF increased CEC proliferation and tube formation but did not increase permeability, the increased proliferation was additive with VEGF.

Conclusion

This study provides insight into the interactions or cross-talk in CEC signalling and indicates that a more efficient approach to regulate intraocular angiogenesis would aim to simultaneously block the actions of multiple growth factors, or the common downstream site in the angiogenesis pathway and this may provide a more sustained treatment response in order to enhance treatment protocols in nAMD.

Conclusion

Commercial interest

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