Diabetic retinopathy (DR) is a chronic microvascular complication of diabetes mellitus (DM). It is a worldwide growing epidemic disease considered to be the leading cause of vision-loss and blindness in people with DM. Redox reactions occurring at the extra- and intracellular levels are essential for the maintenance of cellular homeostasis. Dysregulation of redox homeostasis are implicated in the onset and development of DR. Thioredoxin1 (TRX1) and Thioredoxin2 (TRX2) are cytoplasmic and mitochondrially localized antioxidant proteins ubiquitously expressed in various cells and control cellular reactive oxygen species (ROS) by reducing the disulfides into thiol groups. Thioredoxin-interacting protein (TXNIP) binds to TRX system and inhibits the active reduced form of TRX through disulfide exchange reaction. Recent studies indicate the association of TRX/TXNIP with redox signal transduction pathways including activation of Nod-like receptor pyrin domain containing protein-3 (NLRP3) inflammasome, apoptosis, autophagy/mitophagy, epigenetic modifications in a redox-dependent manner. Thus, it is important to gain a more in-depth understanding about the cellular and molecular mechanisms that links redoxisome and ER/Mitochondrial dysfunction to drive the progression of DR. The purpose of this review is to provide a mechanistic understanding of the complex molecular mechanisms and pathophysiological roles associated with redoxisome, the TRX/TXNIP redox signaling complex under oxidative stress in the development of DR. Also, the molecular targets of FDA approved drugs and clinical trials in addition to effective antioxidant strategies for the treatment of diabetic retinopathy are reviewed.
Keywords: Diabetic retinopathy; Epigenetic modifications; Inflammasome; Redox homeostasis; Redoxisome.
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