Vascular Complications and Diabetes: Current Therapies and Future Challenges

Figure 1

Schematic representation of the progression of diabetic retinopathy. Pericytes interact directly with the normal retinal capillary endothelium (a) within the basement membrane via close contacts and gap junctions ensuring basal tone a(i) and growth arrest a(ii). Persistent hyperglycemia leads to RhoGTPase induction of pericyte contraction b(i) causing reversal of EC growth arrest b(ii) and disrupted matrix contact b(iii) prior to or in the absence of pericyte death/dropout. Basement membrane thickening and leaky, narrow capillaries contribute to thrombosis, ischemia, and the first detectible abnormalities of NPDR. In response to the resultant hypoxia, soluble mediators of angiogenesis, such as VEGF, are released to develop collateral nutrient supply by forming nascent capillary tubes (c). These new blood vessels are highly permeable and fragile and disrupt easily causing hemorrhage and the vision loss characteristic of PDR (d).