Work

High-fat diet disrupts retinal vessel reactivity and redox balance

Year: 2026

Type: article

Abstract: Background A high-fat diet (HFD) is a major public health concern associated with vascular dysfunction and systemic pathological alterations, often linked to oxidative stress and redox imbalance. However, its effects on the retinal microvasculature remain incompletely understood. Objective This study tested the hypothesis that prolonged HFD exposure induces endothelial dysfunction in retinal arterioles. Methods Mice were fed an HFD for 18 weeks, while age-matched controls received a normal chow diet. Retinal arteriole reactivity to changes in intraluminal pressure and vasoactive agents was assessed in vitro . Reactive oxygen species (ROS) production was quantified in retinal cryosections using dihydroethidium staining. Expression of redox- and inflammation-related genes was analyzed in retinal explants by quantitative real-time PCR. Protein expression of key signaling molecules was evaluated by immunofluorescence microscopy. Results Retinal arterioles from HFD-fed mice exhibited attenuated responses to increased intraluminal pressure and impaired endothelium-dependent vasodilation to acetylcholine. ROS levels were elevated in retinal tissue following HFD exposure. Gene expression analysis revealed upregulation of hypoxia- and redox-related markers, including HIF-1α, VEGF-A, and NOX2, as well as the proinflammatory cytokine TNF-α and antioxidant enzyme catalase. Immunofluorescence staining demonstrated increased expression of the receptor for advanced glycation endproducts (RAGE) and NOX2. Conclusion Chronic HFD exposure induces endothelial dysfunction in the retinal microvasculature, associated with increased oxidative stress and altered redox signaling. These findings provide mechanistic insight into the impact of diet-induced metabolic stress on retinal vascular function.

Source: Frontiers in Physiology

DOI: 10.3389/fphys.2026.1869067