Low-Luminance Blue Light-Enhanced Phototoxicity in A2E-Laden RPE Cell Cultures and Rats
Low-Luminance Blue Light-Enhanced Phototoxicity in A2E-Laden RPE Cell Cultures and Rats
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DOI：
10.3390/ijms20071799
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发表时间：
2019-04-11
影响因子：
5.6
通讯作者：
Cheng, Yu-Wen
中科院分区：
文献类型：
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作者：
Lin, Cheng-Hui;Wu, Man-Ru;Cheng, Yu-Wen
N-retinylidene-N-retinylethanolamine（A2 E）和其他bisretinoids是脂褐素的组分，并在视网膜色素上皮（RPE）细胞中积累-这些加合物在视网膜变性的发病机制中被识别。此外，蓝色发光二极管（LED）光（BLL）诱导的视网膜毒性在视网膜变性中起重要作用。在这里，我们证明了低亮度BLL增强A2 E负载的RPE细胞和大鼠的光毒性。将RPE细胞进行合成A2 E，并通过测量裂解的半胱天冬酶-3水平来检查BLL对凋亡生物标志物活化的影响。BLL调节A2 E负载的RPE细胞中的闭锁小带1（ZO-1）的蛋白表达和细胞旁通透性。在短期BLL暴露后，还筛选了早期炎症和血管生成基因。在这项研究中，我们开发了一种大鼠模型，用于A2 E治疗，有或没有BLL暴露21天。BLL暴露引起眼底损害，视网膜总厚度降低，并引起视网膜神经元转导损伤，这与体外数据一致。我们认为BLL和A2 E在视网膜中积累的协同作用增加了视网膜变性的风险。这些结果有助于阐明BLL/A2 E和血管生成/凋亡机制之间的关联，以及进一步的治疗策略。
N-retinylidene-N-retinylethanolamine (A2E) and other bisretinoids are components of lipofuscin and accumulate in retinal pigment epithelial (RPE) cells-these adducts are recognized in the pathogenesis of retinal degeneration. Further, blue light-emitting diode (LED) light (BLL)-induced retinal toxicity plays an important role in retinal degeneration. Here, we demonstrate that low-luminance BLL enhances phototoxicity in A2E-laden RPE cells and rats. RPE cells were subjected to synthetic A2E, and the effects of BLL on activation of apoptotic biomarkers were examined by measuring the levels of cleaved caspase-3. BLL modulates the protein expression of zonula-occludens 1 (ZO-1) and paracellular permeability in A2E-laden RPE cells. Early inflammatory and angiogenic genes were also screened after short-term BLL exposure. In this study, we developed a rat model for A2E treatment with or without BLL exposure for 21 days. BLL exposure caused fundus damage, decreased total retinal thickness, and caused neuron transduction injury in the retina, which were consistent with the in vitro data. We suggest that the synergistic effects of BLL and A2E accumulation in the retina increase the risk of retinal degeneration. These outcomes help elucidate the associations between BLL/A2E and angiogenic/apoptotic mechanisms, as well as furthering therapeutic strategies.