FIG. 2.

Pathways for generation of ROS in the lens. Normal electron transport and activity of cytochrome P450 (P450) can generate ·O₂⁻· The NADPH oxidase complex, which assembles with participation of Rac GTPases and is associated with activation of plasma membrane receptors (R) by extracellular signals (e.g., growth factors), can also generate ·O₂⁻· Growth factor receptors may also be activated by UV radiation-generated reactive oxygen species (ROS). H₂O₂ within the cell can be produced by the activity of superoxide dismutase (SOD) on ·O₂⁻ or it can originate by diffusion through the plasma membrane from the aqueous humor. H₂O₂ can also be generated by ascorbate and molecular oxygen in the presence of ferric ions. Reaction of H₂O₂ with metal ions (M+) can generate other ROS including ·OH or ·O₂⁻ through the Fenton reaction. H₂O₂ can be decomposed enzymatically by GSH-dependent peroxidases (GSHPx) or catalase, and nonenzymatically by reduced glutathione (GSH).