Slit-Robo Signaling in Ocular Angiogenesis
Slit-Robo signaling was firstly discovered as a major repellent pathway at the midline of the central nervous system. Intense investigation found that this pathway also plays an important role in other biological process including angiogenesis. Robo4 is the vascular endothelial cell specific member of Robo family. It was found that Slit-Robo signaling can inhibit endothelial cell migration, tube formation and vascular permeability. Slit-Robo signaling also plays an important role in embryonic and tumor angiogenesis. In animal model of ocular angiogenesis, addition of Slit inhibited laser induced choroidal neovascularization, oxygen induced retinopathy and VEGF induced retinal permeability in a Robo4 dependent manner. Recent data demonstrates that Robo1 and Robo4 form a heterodimer in endothelial cells, The role of this heterodimer in counteracting VEGF signaling is unknown. Further investigation is required to better understand Slit-Robo signaling and develop novel therapy for angiogenesis.
KeywordsVascular Endothelial Growth Factor Proliferative Diabetic Retinopathy Choroidal Neovascularization Endothelial Cell Migration Retinal Vasculature
We thank the following support to HC: Kaisi Funds at Sun Yat-sen University, JSIEC Starting grants; to ST: National Key Science and Technology Project from ‘Tenth Five-Year Plan’ of China, National Natural Science Foundation of China; to KZ: National Institutes of Health Grants R01EY14428, R01EY14448, P30EY014800, and GCRCM01-RR00064, Foundation Fighting Blindness, the Macular Vision Research Foundation, Veterans Affairs Merit Award, and Research to Prevent Blindness to NRL: the Ruth L. Kirschstein National Research Service Award.