Neuroprotective effect of bilberry extract in a murine model of photo-stressed retina.
Neuroprotective effect of bilberry extract in a murine model of photo-stressed retina.
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DOI：
10.1371/journal.pone.0178627
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Ozawa Y
中科院分区：
文献类型：
--
作者：
Osada H;Okamoto T;Kawashima H;Toda E;Miyake S;Nagai N;Kobayashi S;Tsubota K;Ozawa Y
过度暴露于光线会促进退行性和致盲性视网膜疾病，例如年龄相关性黄斑变性和视网膜色素变性。然而，光诱导的视网膜变性的潜在机制尚未完全了解，并且尚未提出可推广的预防性干预措施。越橘提取物是一种富含抗氧化剂的补充剂，可改善眼部症状。然而，其对光应激视网膜的影响尚未阐明。在这项研究中，我们研究了越橘提取物对光应激小鼠视网膜的神经保护作用。通过Balb/c小鼠（750 mg/kg体重）的胃管口服给予越橘提取物，减弱了由暗视和视光视网膜电图记录的光诱导的视觉功能损害，暗视和视光视网膜电图显示各自的视杆和视锥感光器功能。越橘提取物还抑制光诱导的光感受器细胞层的凋亡和杆和锥光感受器外节的缩短。光诱导的活性氧（ROS），氧化和内质网（ER）应激标志物的水平，通过实时逆转录聚合酶链反应测定，降低了越桔提取物治疗。N-乙酰基-L-半胱氨酸（一种众所周知的抗氧化剂）减少ROS也能抑制ER应激。免疫组化分析显示，激活转录因子4表达的ER应力的存在下，在视网膜中，至少在部分，在Müller神经胶质细胞。光诱导的视网膜色素上皮细胞紧密连接的破坏也减弱了越桔提取物，抑制氧化应激标志物，虽然ER应激标志物没有被抑制。我们的研究结果表明，越桔提取物衰减光诱导的细胞凋亡和视觉功能障碍最有可能，至少部分，通过ROS减少，和随后的ER应力衰减在视网膜。这项研究有助于了解光应激的机制，并有助于开发一种新的，潜在的有用的治疗方法，使用越桔提取物预防视网膜光损伤。
Excessive exposure to light promotes degenerative and blinding retinal diseases such as age-related macular degeneration and retinitis pigmentosa. However, the underlying mechanisms of photo-induced retinal degeneration are not fully understood, and a generalizable preventive intervention has not been proposed. Bilberry extract is an antioxidant-rich supplement that ameliorates ocular symptoms. However, its effects on photo-stressed retinas have not been clarified. In this study, we examined the neuroprotective effects of bilberry extract against photo-stress in murine retinas. Light-induced visual function impairment recorded by scotopic and phototopic electroretinograms showing respective rod and cone photoreceptor function was attenuated by oral administration of bilberry extract through a stomach tube in Balb/c mice (750 mg/kg body weight). Bilberry extract also suppressed photo-induced apoptosis in the photoreceptor cell layer and shortening of the outer segments of rod and cone photoreceptors. Levels of photo-induced reactive oxygen species (ROS), oxidative and endoplasmic reticulum (ER) stress markers, as measured by real-time reverse transcriptase polymerase chain reaction, were reduced by bilberry extract treatment. Reduction of ROS by N-acetyl-L-cysteine, a well-known antioxidant also suppressed ER stress. Immunohistochemical analysis of activating transcription factor 4 expression showed the presence of ER stress in the retina, and at least in part, in Müller glial cells. The photo-induced disruption of tight junctions in the retinal pigment epithelium was also attenuated by bilberry extract, repressing an oxidative stress marker, although ER stress markers were not repressed. Our results suggest that bilberry extract attenuates photo-induced apoptosis and visual dysfunction most likely, and at least in part, through ROS reduction, and subsequent ER stress attenuation in the retina. This study can help understand the mechanisms of photo-stress and contribute to developing a new, potentially useful therapeutic approach using bilberry extract for preventing retinal photo-damage.