Testing a novel target for anti-angiogenesis thera.. (ANGIOBLOCK)
Testing a novel target for anti-angiogenesis therapy in the eye
Start date: Oct 28, 2013,
End date: Oct 27, 2014
"Age-related macular degeneration (AMD) is a retinal disease characterized by central vision loss produced mainly by new vessels formed from choroidal capillaries (choroidal neovascularization, CNV). Current therapies are directed to inhibit angiogenesis by blocking vascular endothelial growth factor (VEGF); however patients need to be retreated given that CNV tends to recur. Furthermore, not all patients respond equally well to the treatment. Moreover, sustained blocking of VEGF may have harmful side effects. It is therefore important to explore alternative molecular targets for the prevention of CNV in AMD. In this project, termed ANGIOBLOCK, we aim to test whether targeting Neuropilin 1 (Nrp1) can prevent CNV in a mouse model. Nrp-1 acts as a co-receptor for several different angiogenic ligands and is therefore an attractive target to block CNV. Nrp1 will be deleted by inducible Cre-lox technology in endothelial cells based on tools developed in the host laboratory. Laser induced CNV lesions will then be assessed in longitudinal in vivo studies, using optical coherence tomography and laser scanning ophthalmoscopy, quantifying lesion size and vascular permeability. In addition, post-mortem analysis will use immunohistochemistry, in situ hybridization and gene expression analysis to assess inflammation and angiogenesis. We expect to observe reduced growth of vascular lesions in mice lacking Nrp1, which would validate this molecule as a drug target to reduce CNV in AMD."
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