Figure 1.

Rac1 activation is regulated by GEFs and GAP. In diabetes Tiam1 and Vav2 are upregulated, and these GEFs activate Rac1 leading to increased Rac1-Nox2-ROS signaling pathway. Furthermore, increase in p66Shc displaces Sos1 from Grb2, leading to Rac1 activation. Hyperglycemia also increases prenylation enzyme FNTA and decreases GDI, that further helps Rac1 translocation to the membrane for Nox2 holoenzyme assembly. Increased ROS production by Nox2 augments mitochondrial damage, leading to capillary cell apoptosis and the development of diabetic retinopathy