Inverse correlation between serum levels of brain-derived neurotrophic factor (BDNF) and HMGB-1 was observed in proliferative diabetic retinopathy patients, and intravitreal administration of HMGB-1 induced decreased BDNF in rat retinas, suggesting that HGMB-1-induced downregulation of BDNF might be a therapeutic target to prevent DR neurodegeneration [61, 63]. This evidence concerns the gene HMGB1 and proliferative diabetic retinopathy.