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Investigating the role of HIFs in myeloid cells during experimental choroidal neovascularisation

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Insight into the mechanism of neovascularisation

Understanding the basis of new vessel formation in the retina is fundamental for the treatment of various conditions. To identify the determinants of neovascularisation, European researchers developed novel mouse models lacking specific molecules.

Fundamental Research

Retinal neovascularisation is a feature of several conditions including diabetes and age-related macular degeneration (AMD). It also occurs in some cases of premature babies treated with high doses of oxygen to support lung development. The formation of new fragile blood vessels commences with an increased release of pro-angiogenic cytokines, including vascular endothelial growth factor (VEGF). In turn, VEGF expression in different cell types in the body is regulated by hypoxia inducible factors (HIFs). Neovascular AMD can be improved by VEGF inhibitors but the incomplete efficiency of the treatment suggests the involvement of additional mechanisms. Researchers of the EU-funded AMD_CNV_HIF (Investigating the role of HIFs in myeloid cells during experimental choroidal neovascularisation) project investigated the role of HIFs in neovascularisation. In this context, they generated transgenic mice lacking the HIF molecules (Hif1α, Hif2α and Von Hippel-Lindau tumour suppressor (Vhl)) specifically in myeloid cells, the principal immune cells implicated in neovascularisation. To recapitulate the events taking place in premature babies placed in high oxygen levels after birth, transgenic mice underwent oxygen-induced retinopathy (OIR). Scientists placed them in a high oxygen chamber for five days before returning them to normal air, and examined their retinas. Their observations indicated that Hif1α and Hif2α in myeloid cells were not essential for neovascularisation. Rather, an increased HIF activity in myeloid cells helped blood vessels to grow faster but in a more controlled fashion. Overall, the results of the AMD_CNV_HIF study provide important insight into the mechanism of neovascularisation. Given that neovascularisation can damage the light-sensing cells of the retina, the generated information could help design novel therapies to prevent loss of sight.


Retinal neovascularisation, VEGF, HIF, AMD_CNV_HIF, Von Hippel-Lindau tumour suppressor

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