Abstract
Human cells utilize oxygen as the source of energy, and show various reactions when they are exposed to the environment with decreased oxygen concentration. These reactions enable the cells to survive under hypoxic conditions, whereas they often accelerate the progression of diseases such as diabetic retinopathy. Vasculature, the pathways for oxygen delivery to peripheral tissues, is sensitive to the changes in surrounding oxygen concentration, and the remodeling of retinal vasculature by hypoxia is known to determine the progression of diabetic retinopathy. Vascular remodeling in diabetic retina includes the angiogenesis and the breakdown of blood-retinal barrier function. Our studies have indicated that the hypoxic induction of vascular endothelial growth factor (VEGF), especially its isoform VEGF165, and membrane-type 1 matrix metalloproteinase (MT1-MMP) in retinal glial cells is responsible for the formation of angiogenic lesion in diabetic retinopathy. On the other hand, the breakdown of barrier function of diabetic retinal vessels is attributable to the hypoxia-induced changes in the expression of a tight junction protein, claudin-5, in endothelial cells. In this review, I summarize the data of our studies on the mechanisms underlying the hypoxic remodeling of vasculature and its involvement in disease progression of diabetic retinopathy.
