Song Delu, Song Jiantao, Wang Chenguang, Li Yafeng, Dunaief Joshua L
The F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, United States.
The F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, United States; Eye Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
Exp Eye Res. 2016 Apr;145:1-9. doi: 10.1016/j.exer.2015.10.005. Epub 2015 Oct 22.
Oxidative stress and inflammation play key roles in the light damage (LD) model of photoreceptor degeneration, as well as in age-related macular degeneration (AMD). We sought to investigate whether Berberine (BBR), an antioxidant herb extract, would protect the retina against light-induced degeneration. To accomplish this, Balb/c mice were treated with BBR or PBS via gavage for 7 days, and then were placed in constant cool white light-emitting diode (LED) light (10,000 lux) for 4 h. Retinal function and degeneration were evaluated by histology, electroretinography (ERG) and optical coherence tomography (OCT) at 7d after LD. Additionally, mRNA levels of cell-type specific, antioxidant, and inflammatory genes were compared 7d after LD. Photoreceptor DNA fragmentation was assessed via the terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) assay. LD resulted in substantial photoreceptor-specific cell death. Histological analysis using plastic sections showed dosing with BBR preserved photoreceptors. The ERG analysis demonstrated functional protection by BBR in rod-b, -a, and cone-b waves. In OCT images, mice receiving PBS showed severe thinning and disorganization of the photoreceptor layer 7 days after LD, whereas mice treated with BBR had significantly less thinning and disorganization. Consistent with OCT results, the mRNA levels of Rho in the NSR, and Rpe65 and Mct3 in the RPE, were significantly higher in mice treated with BBR. The numbers of TUNEL-positive photoreceptors were significantly decreased in BBR-treated mice. The retinal mRNA levels of oxidative stress genes, the number of microglia/macrophages, and the malondialdehyde (MDA) immunolabeling were significantly lower in BBR-treated mice compared to controls 48 h after LD, which indicates oxidative stress was reduced by BBR in light-damaged eyes. In conclusion, systemic BBR is protective against light-induced retinal degeneration associated with diminished oxidative stress in the retina. These results suggest that BBR may be protective against retinal diseases involving oxidative stress.
氧化应激和炎症在光感受器变性的光损伤（LD）模型以及年龄相关性黄斑变性（AMD）中起着关键作用。我们试图研究小檗碱（BBR）这种抗氧化草药提取物是否能保护视网膜免受光诱导的变性。为实现这一目的，通过灌胃法给Balb/c小鼠施用BBR或PBS，持续7天，然后将其置于恒定的冷白色发光二极管（LED）光（10,000勒克斯）下照射4小时。在光损伤后7天，通过组织学、视网膜电图（ERG）和光学相干断层扫描（OCT）评估视网膜功能和变性情况。此外，在光损伤后7天比较细胞类型特异性、抗氧化和炎症基因的mRNA水平。通过末端脱氧核苷酸转移酶dUTP缺口末端标记（TUNEL）试验评估光感受器DNA片段化情况。光损伤导致大量光感受器特异性细胞死亡。使用塑料切片进行的组织学分析显示，施用BBR可保留光感受器。ERG分析表明，BBR对视杆细胞b波、a波和视锥细胞b波具有功能保护作用。在OCT图像中，接受PBS处理的小鼠在光损伤7天后显示光感受器层严重变薄和结构紊乱，而用BBR处理的小鼠变薄和结构紊乱程度明显较轻。与OCT结果一致，在接受BBR处理的小鼠中，神经感觉视网膜（NSR）中Rho以及视网膜色素上皮（RPE）中Rpe65和Mct3的mRNA水平显著更高。在接受BBR处理的小鼠中，TUNEL阳性光感受器数量显著减少。与对照组相比，在光损伤后48小时，接受BBR处理的小鼠视网膜氧化应激基因的mRNA水平、小胶质细胞/巨噬细胞数量以及丙二醛（MDA）免疫标记均显著降低，这表明BBR可减轻光损伤眼中的氧化应激。总之，全身性BBR可保护视网膜免受与视网膜氧化应激减轻相关的光诱导变性。这些结果表明，BBR可能对涉及氧化应激的视网膜疾病具有保护作用。
