Resveratrol as a multitarget modulator in diabetic retinopathy: a systematic review of in vitro and in vivo studies.

backgroundResveratrol (RSV) has been extensively investigated for its antioxidant and anti-inflammatory properties across various disease settings; however, its upstream mechanisms in diabetic retinopathy (DR) remain insufficiently characterized. Given that early DR involves oxidative stress, mitochondrial disruption, and microglia-associated inflammatory amplification, this systematic review aims to synthesize preclinical evidence on how RSV influences these early molecular and cellular events in diabetic retinal models.

methodsA systematic search of PubMed, EBSCO, and ProQuest identified in vitro and in vivo studies examining RSV in diabetes-induced retinal disease. Eligible studies evaluated mechanistic outcomes related to oxidative stress, inflammation, mitochondrial function, or neurovascular integrity. Risk of bias was assessed using SYRCLE’s tool for in vivo studies and QUIN-based criteria for in vitro studies.

resultsTwenty studies met inclusion criteria. RSV consistently activated SIRT1 and improved mitophagy and mitochondrial dynamics, leading to reduced ROS-mediated inflammatory activation. RSV also modulated apoptotic pathways by suppressing caspase activity and enhancing SIRT1/PGC-1α–associated survival signalling. Antioxidant defences were strengthened through Nrf2/HO-1 activation, increasing endogenous antioxidant capacity and lowering oxidative injury markers. The most prominent and consistent finding was RSV’s strong anti-inflammatory effect, characterized by reduced TNF-α, IL-6, and IL-1β, inhibition of NF-κB and HMGB1 signaling, and attenuation of microglia-driven inflammatory amplification, supporting a shift toward an anti-inflammatory signaling profile. In vivo studies generally used daily doses ≥ 10 mg/kg, with longer durations producing more consistent neuroinflammatory improvement.

conclusionRSV exerts broad protective actions in DR by modulating mitochondrial function, inflammation, oxidative stress, and angiogenic signaling. With its upstream, multitarget profile, RSV represents a promising adjunctive or early-stage therapeutic candidate. Clinical studies are needed to establish optimal dosing, delivery methods, and translational efficacy in human DR. CLINICAL TRIAL NUMBER: Not applicable.