Critical factors driving diabetic retinopathy pathogenesis and a promising interventional strategy

Diabetic retinopathy (DR) is a common diabetes complication possibly leading to vision loss if not under appropriate control. By reviewing factors and pathways associated with DR pathogenesis, and classifying current DR treatment strategies according to their mechanisms of actions, we identify hyperglycaemia as the primary factor driving DR development towards sustained inflammation, and hypoxia as the external stimuli switching non-proliferative DR to the proliferative state for neovascularization; we emphasize the pivotal roles of energy and oxygen sensors AMP-activated protein kinase and hypoxia-inducible factor in marking these two critical events during DR pathogenesis; and, importantly, we propose the possible use of cold atmospheric plasma (CAP), being composed of a cocktail of reactive oxygen and nitrogen species with multifaceted medical efficacies, as an adjuvant therapy for treating DR. Our views on current and innovative interventional approaches for DR management are based on the identified factors driving DR staging and progression, as well as demonstrated efficacies of CAP in reducing blood glucose levels and alleviating hypoxia if under appropriate dosing control. Our work may open a new paradigm towards the establishment of effective receipts for resolving DR and enlarge medical scenarios feasible for CAP to be translated into the clinics.