叶黄素和玉米黄质异构体可减少 色素性视网膜炎 小鼠模型中的光感受器变性。
Lutein and Zeaxanthin Isomers Reduce Photoreceptor Degeneration in the Mouse Model of Retinitis Pigmentosa.
机构信息
Department of Ophthalmic Research, Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.
Department of Ophthalmology, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA.
出版信息
Biomed Res Int. 2018 Dec 17;2018:4374087. doi: 10.1155/2018/4374087. eCollection 2018.
PURPOSE
Lutein, RR-zeaxanthin, and RS-zeaxanthin (L-Z) are antioxidants which can reduce endoplasmic reticulum stress (ERS) and oxidative stress (OS), and ameliorate neurodegenerative diseases. However, their treatment effect in the () mouse model of retinitis pigmentosa (RP) and the underlying cellular mechanisms have not been studied. ERS is an important factor which causes photoreceptor apoptosis. The aim of the current project is to test the treatment effect of L-Z in mice and to investigate the underlying molecular mechanisms of ERS.
METHODS
L-Z (Lutemax 2020, 10 mg/kg) diluted in sunflower oil (SFO, 1 mg/ml) or the same volume of SFO was administrated via gavage from postnatal day 6 (P6) to P20 daily in L-Z group (n=5) or SFO group (n=6) of mice. At P21, electroretinography (ERG) was performed to show the functional change of retinas. 78 kDa glucose-regulated protein (GRP78) and endoplasmic reticulum protein 29 (ERp29) were tested by western blot and immunostaining.
RESULTS
The ERG amplitudes were larger in the L-Z group than those of the SFO group in all flash luminances of dark-adapted and light-adapted ERG (all < 0.01). Western blot revealed that GRP78 in the retinas of the L-Z group was significantly downregulated compared to that of the SFO group ( < 0.01). Meanwhile, the retinal ERp29 protein was significantly upregulated in the L-Z treatment group than that of the SFO group ( < 0.01).
CONCLUSIONS
L-Z provide protection to the photoreceptors of mouse model of RP, which is probably associated with the reduction of ERS.
目的
叶黄素、RR-玉米黄质和 RS-玉米黄质（L-Z）是抗氧化剂，可减少内质网应激（ERS）和氧化应激（OS），并改善神经退行性疾病。然而，它们在色素性视网膜炎（RP）模型鼠中的治疗效果及其潜在的细胞机制尚未得到研究。ERS 是引起光感受器细胞凋亡的一个重要因素。本项目旨在研究 L-Z 在 （）模型鼠中的治疗效果，并探讨 ERS 的潜在分子机制。
方法
L-Z（Lutemax 2020，10mg/kg）用葵花籽油（SFO，1mg/ml）稀释，或用相同体积的 SFO，从出生后第 6 天（P6）到第 20 天每天通过灌胃给药，L-Z 组（n=5）或 SFO 组（n=6）。在 P21 时，进行视网膜电图（ERG）检查以显示视网膜功能变化。用 Western blot 和免疫组化检测 78kDa 葡萄糖调节蛋白（GRP78）和内质网蛋白 29（ERp29）。
结果
暗适应和明适应 ERG 的所有闪光亮度下，L-Z 组的 ERG 振幅均大于 SFO 组（均 <0.01）。Western blot 显示，与 SFO 组相比，L-Z 组视网膜中的 GRP78 明显下调（ <0.01）。同时，L-Z 处理组的视网膜 ERp29 蛋白明显上调（ <0.01）。
结论
L-Z 为 RP 模型鼠的光感受器提供了保护，这可能与 ERS 的减少有关。
Zotero 插件