Thus, as shown in Figure 1, high homocysteine activates various pathways associated with mitochondrial damage and diabetic retinopathy, the activation of MMP-9 by homocysteine accelerates mitochondrial damage, and the inhibition of the transcriptional activity of Nrf2 compromises the defense system’s ability to overcome the increased oxidative stress. The gene discussed is MMP9; the disease is diabetic retinopathy.