Abstract
In diabetic retinopathy (DR), high blood glucose drives chronic oxidative stress and inflammation that trigger alterations of the neurovascular balance finally resulting in vascular abnormalities and retinal cell death, which converge towards altered electroretinogram (ERG). In the last years, a growing body of preclinical evidence has suggested that nutrients with anti-inflammatory/antioxidant properties can be able to hamper DR progression since its very early stages. In the present study, we used a streptozotocin-induced rat model of DR, which mimics most aspects of the early stages of human DR, to test the preventive efficacy of a novel compound containing cyanidin-3-glucoside (C3G), verbascoside and zinc as nutrients with antioxidant and anti-inflammatory properties. Western blot, immunofluorescence and electroretinographic analyses demonstrated a dose-dependent inhibition of oxidative stress- and inflammation-related mechanisms, with a significant counterpart in preventing molecular mechanisms leading to DR-associated vasculopathy and its related retinal damage. Preventive efficacy of the compound on dysfunctional a- and b-waves was also demonstrated by electroretinography. The present demonstration that natural compounds, possibly as a consequence of vascular rescue following ameliorated oxidative stress and inflammation, may prevent the apoptotic cascade leading to ERG dysfunction, adds further relevance to the potential application of antioxidants as a preventive therapy to counteract DR progression.
Highlights
Diabetic retinopathy (DR) is a leading cause of acquired visual impairment in developed countries
We investigated the efficacy of a compound including C3G, verbascoside and zinc using the chemically induced streptozotocin (STZ) rat model of diabetes, which has been routinely used in preclinical studies and therapeutic drug investigations
vascular endothelial growth factor (VEGF) accumulation induced by high blood glucose triggers major inflammatory processes and several drugs are already approved in clinical practice to handle diabetic macular oedema (DME)
Summary
Diabetic retinopathy (DR) is a leading cause of acquired visual impairment in developed countries. The onset of relevant clinical signs of DR corresponds to advanced stages of the disease that marks a point of no return (Sinclair and Schwartz, 2019). These aspects render the clinical management of DR a challenging topic. Antioxidants Supplement and Diabetic Retinopathy and feeds the research of treatment approaches to intervene on the early stages of the disease in order to prevent or delay DR progression. Prolonged exposure to high glucose leads to metabolic stress that affects the BRB and the highly specialized neural connections, responsible for vision processes (Feng et al, 2012; Mi et al, 2014). Antioxidant defenses are overwhelmed by ROS accumulation producing the onset of oxidative stress (Kowluru and Chan, 2007)
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