Figure 9.

Possible mechanisms of neurovascular degeneration after retinal I/R. Cartoon showing possible sources of superoxide and other ROS, which can increase A2 expression. A2 upregulation depletes l-arginine needed for NO production by NOS. This leads to NOS uncoupling with production of more superoxide, which reacts with NO to form ONOO⁻, further increasing ROS levels. A2 upregulation can also increase SMO expression and activity, further increasing ROS production. These mechanisms can activate cell death pathways leading to neurovascular degeneration after retinal I/R insult. O₂^.−, superoxide; NOX2, NADPH oxidase 2; SMO, spermine oxidase; ONOO-, peroxynitrite; NOS, nitric oxide synthase; NO, nitric oxide. Question marks point to potential mechanisms that will be investigated in future studies