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Blood vessels that supply the inner portion of the retina are extensively reorganized during development. The vessel regression, sprouting angiogenesis, vascular remodelling and vessel differentiation events involved critically depend on cell–cell signalling between different cellular components such as neurons, glia, endothelial cells, pericytes and immune cells. Studies in mice using transgenic and gene deletion approaches have started to unravel the genetic basis of some of these signalling pathways and have lead to a much improved understanding of the molecular mechanisms controlling retinal blood vessel behaviour both during development and under pathological conditions. Such insight will provide the basis of future therapeutic approaches aimed at manipulating retinal blood vessels.