Department of Ophthalmology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
Mol Med Rep. 2019 Jan;19(1):382-390. doi: 10.3892/mmr.2018.9634. Epub 2018 Nov 8.
To investigate the function of progranulin on the retina under hypoxic conditions, 8‑week‑old C57BL/6 mice were divided into normal condition and hypoxic condition groups (n=24 mice/group). The hypoxia model was established through intravitreal injection of 9 mM cobalt chloride. Subsequently, 10 mM progranulin and an equal amount of PBS were injected into the right and left eyes, respectively. Photoreceptor function was examined using electroretinogram (ERG) analysis. Morphological alterations were examined using immunofluorescence co‑localization, retinal vascular inflammation was examined using the leukostasis assay, and signaling pathways were screened using immunoblotting. The results revealed that ERG amplitude was significantly lower under hypoxic conditions compared with under normal conditions. Furthermore, the amplitude was significantly reduced in the PBS‑injected eyes compared with in the progranulin‑injected eyes. Morphological examination demonstrated that the number of rods in the PBS‑injected eyes was decreased compared with in the progranulin‑injected eyes under hypoxic conditions. In addition, the arrangement of the cones was sparse and the morphology of the outer segments was short and small. Although the number of adherent leukocytes in the progranulin‑injected eyes was higher in the hypoxic mice compared with in those under normal conditions, the number was only 52.31% of the number detected in the PBS‑injected eyes. Analysis of the signaling pathways demonstrated that the protective effects of progranulin on retinas under hypoxic conditions were regulated by the Toll‑like receptor 4 (TLR4)‑NADPH oxidase 4 (NOX4) pathway, instead of the caspase and Wnt/β‑catenin pathways. In conclusion, progranulin exerted protective effects on the function and morphology of photoreceptors in a hypoxic environment, and could reduce retinal vascular inflammation, through inhibition of the TLR4‑NOX4 pathway.
为了研究颗粒蛋白聚糖在缺氧条件下对视网膜的作用，将 8 周龄 C57BL/6 小鼠分为正常组和缺氧组（每组 24 只小鼠）。通过玻璃体内注射 9mM 氯化钴建立缺氧模型。随后，分别向右眼和左眼注射 10mM 颗粒蛋白聚糖和等量 PBS。通过视网膜电图（ERG）分析检测光感受器功能。通过免疫荧光共定位检测形态改变，通过白细胞停滞试验检测视网膜血管炎症，通过免疫印迹筛选信号通路。结果表明，与正常条件相比，缺氧条件下 ERG 幅度明显降低。此外，与颗粒蛋白聚糖注射眼相比，PBS 注射眼的幅度明显降低。形态学检查表明，与颗粒蛋白聚糖注射眼相比，缺氧条件下 PBS 注射眼的杆状细胞数量减少。此外，锥体排列稀疏，外节形态短小。虽然缺氧小鼠中颗粒蛋白聚糖注射眼的黏附白细胞数量高于正常条件下的，但仅为 PBS 注射眼的 52.31%。信号通路分析表明，颗粒蛋白聚糖对缺氧条件下视网膜的保护作用是通过 Toll 样受体 4（TLR4）-NADPH 氧化酶 4（NOX4）通路调节的，而不是 caspase 和 Wnt/β-连环蛋白通路。总之，颗粒蛋白聚糖在缺氧环境下对光感受器的功能和形态具有保护作用，并可通过抑制 TLR4-NOX4 通路减少视网膜血管炎症。
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