Aberrant neovascularisation contributes to diseases such as cancer, blindness and atherosclerosis and is the consequence of inappropriate angiogenic signalling. While many regulators of pathogenic angiogenesis have been identified, our understanding of this process is incomplete. Here we explored the transcriptome of retinal microvessels isolated from mouse models of retinal disease that exhibit vascular pathology and uncovered an up-regulated gene, leucine-rich alpha-2-glycoprotein-1 (Lrg1), of previously unknown function. We show that in the presence of TGFβ1, LRG1 is mitogenic to endothelial cells and promotes angiogenesis. Mice lacking Lrg1 develop a mild retinal vascular phenotype but exhibit a significant reduction in pathological ocular angiogenesis. LRG1 binds directly to the TGFβ accessory receptor endoglin which, in the presence of TGFβ1, results in promotion of the pro-angiogenic Smad1/5/8 signalling pathway. LRG1 antibody blockade inhibits this switch and attenuates angiogenesis. These studies reveal a novel regulator of angiogenesis that mediates its effect through modulating TGFβ signalling.

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Despite different aetiologies, age-related macular degeneration and most inherited retinal disorders culminate in the same final common pathway, the loss of photoreceptors. There are few treatments and none reverse the loss of vision. Photoreceptor replacement by transplantation is proposed as a broad treatment strategy applicable to all degenerations. Recently, we demonstrated restoration of vision following rod-photoreceptor transplantation into a mouse model of stationary night-blindness, raising the critical question of whether photoreceptor replacement is equally effective in different types and stages of degeneration. We present a comprehensive assessment of rod-photoreceptor transplantation across six murine models of inherited photoreceptor degeneration. Transplantation is feasible in all models examined but disease type has a major impact on outcome, as assessed both by the morphology and number of integrated rod-photoreceptors. Integration can increase (Prph2

These findings suggest that the lack of Ccl2 leads to a monocyte/macrophage-trafficking defect during aging and to an impaired recruitment of these cells to sites of laser injury. Other, previously described features of Ccl2(-/-) mice that are similar to AMD may be the result of aging alone.