Oxidative Stress-Related Mechanisms and Antioxidant Therapy in Diabetic Retinopathy

Figure 5

The mechanisms of Ras and Rho proteins in DR. High glucose activates H-Ras via ROS and/or other classical pathways, which contains two steps: H-Ras translocates from the cytosol to the membrane and H-Ras binds to GTP. The former can be inhibited by simvastatin; the latter can be activated by guanine nucleotide exchange factor (GNEF). After that, Raf-1 also can be activated by translocation to the membrane and binding with H-Ras, thus initiating the Ras/Raf/MEK/ERK pathway. On the other hand, Rho can be activated by high glucose and elevate the level of TGF-β, thus promoting the Rho/ROCK pathway. Both of these pathways lead to increased levels of various cytokines involved in DR. ECM, extracellular matrix; eNOS, endothelial nitric oxide synthase; ET-1, endothelin-1; ERK 1/2, extracellular signal regulated kinases 1/2; ICAM-1, intercellular adhesion molecule-1; GNEF, guanine nucleotide exchange factor; MEK 1/2, mitogen-activated protein kinase kinase 1/2; MLC, myosin light chain; MMP-9, matrix metalloproteinase-9; NF-κB, nuclear factor-κB; ROCK, Rho-kinase; TGF-β, transforming growth factor-β; VEGF, vascular endothelial growth factor.