Novel therapeutic targets in diabetic retinopathy

Abstract

AbstractThe present armatorium for the prevention or treatment of diabetic retinopathy (DR) comprises modulation of systemic factors, laser, surgical approaches, anti‐VEGF agents and corticosteroids. In designing new therapies, the clinical targets of the various stages of DR should be clearly defined: these are vasoregression in pre‐clinical DR, blood‐retinal barrier loss, inflammation and retinal ischemia in macular edema, and angiogenesis and fibrosis in proliferative DR. With regards to early vasoregression, glucose‐induced alterations in biochemical pathways, growth factors such as CTGF and Angiopoeitin‐2, and leukocyte adhesion are under investigation as targets for prevention, whereas stem cell approaches have been suggested to allow repair of already degenerated retinal capillaries. For non‐proliferative DR and macular edema, inflammatory targets such as TNF‐alpha, IL‐6, IL‐10 and the Kallikrein‐Kinin system are under investigation as targets for alternative or adjunct treatments for anti‐VEGF and laser. However, the growing understanding of the cellular mechanisms of blood‐retinal barrier loss may also allow for more directed therapies aimed at the paracellular or transcellular pathways of leakage, while new neuroprotective agents may restrict the ongoing neuronal loss in this stage of DR. For inhibition of angiogenesis in proliferative DR, several novel agents are available to enter clinical development. Finally, recent new insights in the pathogenesis of the angio‐fibrotic switch and scarring have identified CTGF and other factors as potential therapeutic targets for prevention of this final blinding phase of DR.