Investigators and Projects
Retinal angiogenesis arises in a number of different diseases and it can have severe sight threatening consequences. Infiltrating myeloid cells play a central role in the regulation of retinal angiogenesis. Understanding the impact that inflammatory regulators such as cytokines have on the behaviour of macrophages and subsequently on angiogenesis is therefore a critical area for research in ocular inflammation. Macrophages play this role through the elaboration of angiogenic growth factors.
Vascular endothelial growth factor (VEGF) family and platelet derived growth factor C (PDGF-CC) are important for vessel development. Inhibiting these growth factors can suppress abnormal retinal and choroidal angiogenic disease, such as age-related macular degeneration (AMD). VEGF signals via receptors on endothelial cells to trigger vascular remodelling. Macrophages modulate the VEGF signalling pathways by a number of different mechanisms, and manipulating macrophage activation has potential in the treatment of retinal vascular neogenesis. PDGF-CC is part of a family of potent mesenchymal cell mitogens and also a potent neuroprotective agent, due to its ability to regulate expression of neuroprotective and apoptotic genes via glycogen synthase kinase (GSK-3beta).
However, targeting single molecules, such as VEGF or PDGF-CC, does not offer a complete solution to the problem of abnormal angiogenesis. Understanding how to combine multiple approaches needs to be determined to ensure effective inhibition on AMD. Projects related to inflammation and angiogenesis aim to understand how myeloid cells contribute to regulate angiogenesis and to investigate potential therapeutic strategy.
Liu, J., Copland, D. A., Horie, S., Wu, W-K., Chen, M., Xu, Y., Paul Morgan, B., Mack, M., Xu, H., Nicholson, L. B. & Dick, A. D. (2013) Myeloid cells expressing VEGF and arginase-1 following uptake of damaged retinal pigment epithelium suggests potential mechanism that drives the onset of choroidal angiogenesis in mice PloS one 8: e72935 doi: 10.1371/journal.pone.0072935
Wu W.K., Llewellyn O.P., Bates D.O., Nicholson L.B. and Dick A.D. (2010) IL-10 regulation of
macrophage VEGF production is dependent on macrophage polarisation and hypoxia
Immunobiology 215:796-803.