Abstract
Diabetic retinopathy (DR) is the leading cause of vision loss among working-age adults. Extensive evidences have documented that oxidative stress mediates a critical role in the pathogenesis of DR. Acrolein, a product of polyamines oxidation and lipid peroxidation, has been demonstrated to be involved in the pathogenesis of various human diseases. Acrolein’s harmful effects are mediated through multiple mechanisms, including DNA damage, inflammation, ROS formation, protein adduction, membrane disruption, endoplasmic reticulum stress, and mitochondrial dysfunction. Recent investigations have reported the involvement of acrolein in the pathogenesis of DR. These studies have shown a detrimental effect of acrolein on the retinal neurovascular unit under diabetic conditions. The current review summarizes the existing literature on the sources of acrolein, the impact of acrolein in the generation of oxidative damage in the diabetic retina, and the mechanisms of acrolein action in the pathogenesis of DR. The possible therapeutic interventions such as the use of polyamine oxidase inhibitors, agents with antioxidant properties, and acrolein scavengers to reduce acrolein toxicity are also discussed.
Highlights
Diabetic retinopathy (DR), a complication of diabetes, is a significant public health issue and the leading cause of vision loss among working-age adults [1]
In vitro studies revealed that injury induced by acrolein was more toxic than reactive oxygen species (ROS) [20,35] and other aldehydes produced during polyamine metabolism [36]
The current review summarizes the existing literature on the various sources of acrolein, the impact of acrolein in the generation of oxidative damage in the diabetic retina, and the mechanisms of acrolein action in the pathogenesis of DR
Summary
Diabetic retinopathy (DR), a complication of diabetes, is a significant public health issue and the leading cause of vision loss among working-age adults [1]. The current therapeutic avenues for DR are anti-VEGF agents, anti-inflammatory drugs, and laser treatment They treat advanced stages of the disease, the vascular damage, and have adverse side effects. In vitro studies revealed that injury induced by acrolein was more toxic than ROS [20,35] and other aldehydes produced during polyamine metabolism [36]. This oxidative damage caused by acrolein leads to mitochondrial dysfunction, membrane disruption, and increased apoptosis [21,37,38]. The current review summarizes the existing literature on the various sources of acrolein, the impact of acrolein in the generation of oxidative damage in the diabetic retina, and the mechanisms of acrolein action in the pathogenesis of DR
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