Dopamine ameliorates hyperglycemic memory-induced vascular dysfunction in diabetic retinopathy

Dopamine is a neurotransmitter that mediates visual function in the retina, and hyperglycemic memory (HGM) is a pivotal phenomenon in the development of diabetic retinopathy (DR); however, the role of dopamine in HGM-induced retinal vascular dysfunction remains unclear. Here, we report a mechanism of HGM-induced retinal vascular dysfunction and the protective effect of dopamine against the HGM-induced DR. HGM induces retinal vascular lesions through persistent oxidative stress, mitochondrial dysfunction, and microvascular abnormalities after blood glucose normalization, and dopamine ameliorates this HGM-induced retinopathy. HGM induced persistent oxidative stress, mitochondrial membrane potential collapse and fission, and adherens junction disassembly and subsequent vascular leakage in the mouse retinas. These persistent hyperglycemic stresses were inhibited by dopamine treatment in human retinal endothelial cells and by intravitreal injection of levodopa in the retinas of HGM mice. Our findings suggest that dopamine alleviates HGM-induced retinal vascular dysfunction by inhibiting persistent mitochondrial dysfunction and microvascular abnormalities.