Mechanistic insights into the role of FOXO in diabetic retinopathy

Diabetes mellitus (DM), a metabolic disorder characterized by insulin-deficiency or insulin-resistant conditions. The foremost microvascular complication of diabetes is diabetic retinopathy (DR). This is a multifaceted ailment mainly caused by the enduring adverse effects of hyperglycaemia. Inflammation, oxidative stress, and advanced glycation products (AGES) are part and parcel of DR pathogenesis. In regulating many cellular and biological processes, the family of fork-head transcription factors plays a key role. The current review highlights that FOXO is a requisite regulator of pathways intricate in diabetic retinopathy on account of its effect on microvascular cells inflammatory and apoptotic gene expression, and FOXO also has the foremost province in regulating cell cycle, proliferation, apoptosis, and metabolism. Blockage of insulin turns into an exaggerated level of glucose in the bloodstream and can upshot into the exaggerated triggering of FOXO1, which can ultimately uplift the production of several factors of apoptosis and inflammation, such as TNF-α, NF-kB, and various others, as well as reactive oxygen species, which can also come up with diabetic retinopathy. The current review also focuses on various therapies which can be used in the future, like SIRT1 signalling, resveratrol, retinal VEGF, etc., which can be used to suppress FOXO over activation and can prevent the progression of diabetic complications viz. diabetic retinopathy.