Description
The retina relies on a dense vascular network to meet its high metabolic demand. Impaired vascular function and insufficient vessel growth are key features of several sight-threatening retinal diseases. Although anti-VEGF therapies are the current gold-standard treatment, a substantial proportion of patients respond poorly, and retinal ischemia remains unresolved due to vessel loss and abnormal vessel regrowth. Neuropilin (NRP) 1, a co-receptor for vascular endothelial growth factor receptor-2 (VEGFR2), is a multifunctional transmembrane receptor protein critical for retinal angiogenesis. However, loss of VEGF binding to NRP1 only mildly impairs retina angiogenesis, suggesting that NRP1 promotes retina vascularisation in a VEGF-independent manner through unidentified ligands. Here, we show that both physiological vascularisation and ischemic neovascularisation are decreased in the retina of mice with a mutation in one of the two adhesion domains in NRP1. This finding suggests that NRP1 can contribute to angiogenesis even under VEGF-neutralising conditions.
Lay Abstract
Background: Diseases such as diabetic retinopathy, age-related macular degeneration, and retinopathy of prematurity cause blindness in part due to blood vessel damage. Current therapeutic approach targeting the vascular endothelial growth factor (VEGF) helps to improve vision by alleviating retinal swelling but does not repair the damaged blood vessels.
Question: Is there another therapeutic target other than VEGF that could enable vascular repair and regeneration?
Methodology: We investigate the molecular mechanisms by which the molecule NRP1 promotes retinal blood vessel growth during normal eye development and in an animal model of ischemic retinopathy. We have discovered a novel NRP1 function that promotes functional new blood vessel growth and may even work under conditions of therapeutic VEGF neutralisation.
Outcomes: Our project will establish whether non-VEGF NRP1 ligands provide novel therapeutic targets for vascular repair and regeneration in ischemic retinopathy.
| Lay Title | Novel therapeutic target for sight-threatening retinopathy instead of anti-VEGF |
|---|---|
| Role | PhD Student |