Department of Ophthalmology, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131, Mainz, Germany.
Department of Pharmacology, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131, Mainz, Germany.
Exp Eye Res. 2024 Jan;238:109727. doi: 10.1016/j.exer.2023.109727. Epub 2023 Nov 14.
Obesity is a significant health concern that leads to impaired vascular function and subsequent abnormalities in various organs. The impact of obesity on ocular blood vessels, however, remains largely unclear. In this study, we examined the hypothesis that obesity induced by high-fat diet produces vascular endothelial dysfunction in the ophthalmic artery. Mice were subjected to a high-fat diet for 20 weeks, while age-matched controls were maintained on a standard diet. Reactivity of isolated ophthalmic artery segments was assessed in vitro. Reactive oxygen species (ROS) were quantified in cryosections by dihydroethidium (DHE) staining. Redox gene expression was determined in ophthalmic artery explants by real-time PCR. Furthermore, the expression of nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2), the receptor for advanced glycation end products (RAGE), and of the lectin-like oxidized low-density-lipoprotein receptor-1 (LOX-1) was determined in cryosections using immunofluorescence microscopy. Ophthalmic artery segments from mice on a high-fat diet exhibited impaired vasodilation responses to the endothelium-dependent vasodilator acetylcholine, while endothelium-independent responses to nitroprusside remained preserved. DHE staining intensity in the vascular wall was notably stronger in mice on a high-fat diet. Messenger RNA expression for NOX2 was elevated in the ophthalmic artery of mice subjected to high fat diet. Likewise, immunostainings revealed increased expression of NOX2 and of RAGE, but not of LOX-1. These findings suggest that a high-fat diet triggers endothelial dysfunction by inducing oxidative stress in the ophthalmic artery via involvement of RAGE and NOX2.
肥胖是一个严重的健康问题，可导致血管功能受损，随后影响到各种器官。然而，肥胖对眼部血管的影响在很大程度上仍不清楚。在这项研究中，我们检验了一个假设，即高脂肪饮食引起的肥胖会导致眼动脉的血管内皮功能障碍。将小鼠喂食高脂肪饮食 20 周，而年龄匹配的对照组则维持在标准饮食。在体外评估分离的眼动脉段的反应性。通过二氢乙啶（DHE）染色在冷冻切片中量化活性氧（ROS）。通过实时 PCR 确定眼动脉外植体中的氧化还原基因表达。此外，通过免疫荧光显微镜在冷冻切片中确定烟酰胺腺嘌呤二核苷酸磷酸氧化酶 2（NOX2）、晚期糖基化终产物（RAGE）受体和凝集素样氧化低密度脂蛋白受体-1（LOX-1）的表达。高脂肪饮食组的小鼠眼动脉段对内皮依赖性血管扩张剂乙酰胆碱的血管舒张反应受损，而对硝普钠的内皮非依赖性反应保持不变。高脂肪饮食组小鼠血管壁中的 DHE 染色强度明显增强。高脂肪饮食组小鼠眼动脉中 NOX2 的信使 RNA 表达升高。同样，免疫染色显示 NOX2 和 RAGE 的表达增加，但 LOX-1 的表达没有增加。这些发现表明，高脂肪饮食通过涉及 RAGE 和 NOX2 的机制，在眼动脉中引发氧化应激，从而引发内皮功能障碍。
