Diabetic retinopathy: new pharmacological targets

Diabetic retinopathy (DR) is a secondary complication of diabetes mellitus and represents the most common cause of irreversible vision loss in working people of industrialized countries. DR is generally considered a microvascular complication of diabetes, although the inflammatory component plays a key role. The main cause of vision loss in diabetic patients with proliferative diabetic retinopathy is the diabetic macular edema (DME), that is responsible to the retinal detachment. DME is mainly caused by new angiogenesis, which is a hallmark of the advanced stage of DR (proliferative diabetic retinopathy, PDR). Retinal neovascularization is principally driven by pro-angiogenic factors (e.g., VEGF-A, PlGF), inflammatory mediators (TNF-α, interleukins, chemokines) and oxidative stress-related elements. Chronic hyperglycemia is the primary causative factor of DR, however, several points of DR etiopathogenesis are still unclear. Many other factors are involved during the early stages of DR such as the retinal hypoxia, that is a trigger of VEGF release in the back of the eye. Up to now, the pharmacological approaches for DR are intravitreal anti-VEGF agents and corticosteroids. However, some patients can be refractory to anti-VEGF therapy, therefore, efforts must be carried out to discover novel pharmacological targets to handle DR. Hereby, the current literature will be revised about novel potential pharmacological targets, with a focus on PlGF, miRNAs and purinergic P2X7 receptor. Future drug development campaigns on these targets might lead to better clinical outcomes, possibly in the early phase of the disease.

Impact statement

Currently, management and treatment of diabetic retinopathy (DR) are characterized by several unmet medical needs. Particularly, early-stage DR lacks of approved therapeutical intervention, and its pathogenesis is multifactorial. Pharmacological research should focus on novel pharmacological targets, that address pathogenetic factors of DR, such as inflammation, oxidative stress and angiogenesis.