Oxidative Stress and Microvascular Alterations in Diabetic Retinopathy: Future Therapies

Abstract

Diabetes is a disease that can be treated with oral antidiabetic agents and/or insulin. However, patients' metabolic control is inadequate in a high percentage of them and a major cause of chronic diseases like diabetic retinopathy. Approximately 15% of patients have some degree of diabetic retinopathy when diabetes is first diagnosed, and most will have developed this microvascular complication after 20 years. Early diagnosis of the disease is the best tool to prevent or delay vision loss and reduce the involved costs. However, diabetic retinopathy is an asymptomatic disease and its development to advanced stages reduces the effectiveness of treatments. Today, the recommended treatment for severe nonproliferative and proliferative diabetic retinopathy is photocoagulation with an argon laser and intravitreal injections of anti-VEGF associated with, or not, focal laser for diabetic macular oedema. The use of these therapeutic approaches is severely limited, such as uncomfortable administration for patients, long-term side effects, the costs they incur, and the therapeutic effectiveness of the employed management protocols. Hence, diabetic retinopathy is the widespread diabetic eye disease and a leading cause of blindness in adults in developed countries. The growing interest in using polyphenols, e.g., resveratrol, in treatments related to oxidative stress diseases has spread to diabetic retinopathy. This review focuses on analysing the sources and effects of oxidative stress and inflammation on vascular alterations and diabetic retinopathy development. Furthermore, current and antioxidant therapies, together with new molecular targets, are postulated for diabetic retinopathy treatment.

PGC-1α, Inflammation, and Oxidative Stress: An Integrative View in Metabolism

“…Several studies have emphasized high ROS levels in diabetic patients and the role of ROS in cellular signaling alteration, which contributes to the development and complications of T2DM [184]. As previously mentioned, mitochondrial dysfunction is associated with T2DM, and this mitochondrial impairment may trigger oxidative stress [164].…”

A Network Pharmacology Based Analysis of The Potential Mechanisms of Compound Danshen Dripping Pill for Treatment of Diabetic Retinopathy

“…[33][34][35] There were still some non-speci c compounds of CDDP at the top of the list (Table 1), which could not be ignored. Polyphenols like quercetin and luteolin have been suggested to be therapeutic for DR. 36 Luteolin from RS is believed to have effects on activating anti-in ammatory, antioxidant responses, neuroprotective effects and regulating relaxation, lipid pro le via acting on multiple signaling pathways. [37][38][39][40][41][42] Taken together, tanshinones and luteolin may be responsible for the effectiveness of CDDP against DR.…”

The Benefits of Flavonoids in Diabetic Retinopathy

“…Protein kinase C (PKC) is a family of cAMP-dependent protein kinases with multiple isoforms. PKC regulation by a rise in oxidative and nitrosative stress can contribute to the redox mechanism-mediated signaling events of the DR pathogenesis in many cellular functions, such as cell survival, migration, growth, proliferation and apoptosis [ 42 ]. PKC-δ is implicated in the apoptosis of capillary cells by increasing the transcriptional expression of the Scr homology-2 domain that contains phosphatase-1 (SHP-1), leading to the dephosphorylation of platelet-derived growth factor receptor-β (PDGFR-β), critical for retinal pericyte survival.…”