網膜血管新生におけるmTOR 経路の意義と治療標的としての可能性

抄録

Pathological angiogenesis contributes to the pathogenesis of vision-threatening retinal diseases, such as and diabetic retinopathy and retinopathy of prematurity. Anti-vascular endothelial growth factor (VEGF) agents are now commonly used to treat the retinal diseases associated with pathological angiogenesis. However, adverse effects associated with the blockade of VEGF signaling, including impairments of normal retinal vascular growth and retinal function, were suggested. The ideal antiangiogenic drugs would target endothelial cells in a proliferative state but would not interfere with quiescent endothelial cells. We recently found that the mTOR pathway is activated in proliferating endothelial cellsbut is inactivated in quiescent endothelial cells within the retinal vasculature. Inhibitors of the mTOR display a narrow-spectrum effect on proliferating endothelial cells in the retina. The ability of mTOR inhibitors to target endothelial cells in a proliferative state may be a favorable trait for safe, effective antiangiogenic therapy in retinal diseases that are driven by pathological angiogenesis.