Serum levels of copper and zinc in diabetic retinopathy: Potential new therapeutic targets (Review)

Diabetic retinopathy (DR) is a microvascular disorder occurring due to the long-term effects of diabetes, leading to vision-threatening damage to the retina. The human body has an elaborate system for managing and regulating the number of key trace metals circulating in the blood and stored cells. Inadequate zinc (Zn) and concurrent excess of copper (Cu) levels are associated with an increased level of oxidative stress, which may aggravate the microvascular lesions in diabetes mellitus. Several studies have revealed a significantly lower serum Zn concentration and increased Cu levels in DR when compared with diabetic patients without retinopathy and normal controls. These abnormalities are correlated with the duration of diabetes and higher levels of HbA1C. Multiple pathological mechanisms are proposed to explain these changes including hyperzincuria associated with polyuria, glycosuria, and proteinuria in diabetic patients, as well as impaired absorption of Zn at the gastrointestinal level. Increased levels of free Cu ions may be attributed to glycation and the release of Cu ions from the Cu-binding sites of proteins. Zn supplements and selective Cu chelators may be useful to alleviate oxidative stress and prevent DR progression.