Tianjin Medical University, Tianjin, China.
Tianjin Key Lab of Ophthalmology and Visual Science, Tianjin Eye Hospital, Tianjin Eye Institute, Tianjin, China.
Sci Rep. 2020 Nov 2;10(1):18601. doi: 10.1038/s41598-020-75576-7.
To investigate the effects of a high-fat diet (HFD) and apolipoprotein E (Apoe) deficiency on retinal structure and function in mice. Apoe KO mice and wild-type C57BL/6J mice were given a low-fat diet (LFD) or a HFD for 32 weeks. Blood glucose, serum lipids, body weight and visceral fat weight were evaluated. Retinal sterol quantification was carried out by isotope dilution gas chromatography-mass spectrometry. The cholesterol metabolism related genes SCAP-SREBP expressions were detected by qRT-PCR. Retinal function was recorded using an electroretinogram. The thickness of each layer of the retina was measured by optical coherence tomography. Fundus fluorescein angiography was performed to detect retinal vasculature changes. Immunohistochemical staining was used to determine the expression of NF-κB, TNF-α and VEGFR2 in the retina among HFD, HFD Apoe, LFD Apoe and WT mice retinas. HFD feeding caused the mice to gain weight and develop hypercholesterinemia, while Apoe abnormalities also affected blood lipid metabolism. Both HFD and Apoe deficiency elevated retinal cholesterol, especially in the HFD Apoe mice. No up-regulated expression of SCAP-SREBP was observed as a negative regulator. Impaired retinal functions, thinning retinas and abnormal retinal vasculature were observed in the peripheral retinas of the HFD and Apoe mice compared with those in the normal chow group, particularly in the HFD Apoe mice. Moreover, the expression of NF-κB in the retinas of the HFD and Apoe mice was increased, together with upregulated TNF-α mRNA levels and TNF-α expression in the layer of retinal ganglion cells of the peripheral retina. At the same time, the expression level of VEGFR2 was elevated in the intervention groups, most notably in HFD Apoe mice. HFD or Apoe gene deletion had certain adverse effects on retinal function and structure, which were far below the combined factors and induced harm to the retina. Furthermore, HFD caused retinal ischemia and hypoxia. Additionally, Apoe abnormality increased susceptibility to ischemia. These changes upregulated NF-κB expression in ganglion cells and activated downstream TNF-α. Simultaneously, they activated VEGFR2, accelerating angiogenesis and vascular permeability. All of the aforementioned outcomes initiated inflammatory responses to trigger ganglion cell apoptosis and aggravate retinal neovascularization.
为了研究高脂肪饮食（HFD）和载脂蛋白 E（Apoe）缺乏对小鼠视网膜结构和功能的影响。apoE KO 小鼠和野生型 C57BL/6J 小鼠分别给予低脂饮食（LFD）或 HFD32 周。评估血糖、血脂、体重和内脏脂肪重量。采用同位素稀释气相色谱-质谱法对视网膜甾醇进行定量。通过 qRT-PCR 检测胆固醇代谢相关基因 SCAP-SREBP 的表达。使用视网膜电图记录视网膜功能。通过光相干断层扫描测量视网膜各层的厚度。进行眼底荧光血管造影以检测视网膜血管变化。免疫组织化学染色检测 HFD、HFD apoE、LFD apoE 和 WT 小鼠视网膜中 NF-κB、TNF-α 和 VEGFR2 的表达。HFD 喂养导致小鼠体重增加和高胆固醇血症，而 apoE 异常也影响血脂代谢。HFD 和 apoE 缺乏均使视网膜胆固醇升高，尤其是 HFD apoE 小鼠。作为负调节剂，未观察到 SCAP-SREBP 的上调表达。与正常饮食组相比，HFD 和 apoE 小鼠的外周视网膜视网膜功能受损、视网膜变薄和视网膜血管异常，尤其是 HFD apoE 小鼠。此外，HFD 和 apoE 小鼠视网膜 NF-κB 表达增加，同时外周视网膜神经节细胞层 TNF-α mRNA 水平和 TNF-α 表达上调。同时，干预组中 VEGFR2 的表达水平升高，尤其是在 HFD apoE 小鼠中。HFD 或 apoE 基因缺失对视网膜功能和结构有一定的不良影响，远远低于联合因素对视网膜的损害。此外，HFD 导致视网膜缺血缺氧。此外，apoE 异常增加了对缺血的易感性。这些变化上调了神经节细胞中 NF-κB 的表达，并激活了下游的 TNF-α。同时，它们激活了 VEGFR2，加速了血管生成和血管通透性。所有这些结果都引发了炎症反应，导致神经节细胞凋亡和视网膜新生血管加重。
