PDF(Pubmed)
Abstract：
Because the selective estrogen receptor modulator tamoxifen was shown to be retina-protective in the light damage and rd10 models of retinal degeneration, the purpose of this study was to test whether tamoxifen is retina-protective in a model where retinal pigment epithelium (RPE) toxicity appears to be the primary insult: the sodium iodate (NaIO3) model. C57Bl/6J mice were given oral tamoxifen (in the diet) or the same diet lacking tamoxifen, then given an intraperitoneal injection of NaIO3 at 25 mg/kg. The mice were imaged a week later using optical coherence tomography (OCT). ImageJ with a custom macro was utilized to measure retinal thicknesses in OCT images. Electroretinography (ERG) was used to measure retinal function one week post-injection. After euthanasia, quantitative real-time PCR (qRT-PCR) was performed. Tamoxifen administration partially protected photoreceptors. There was less photoreceptor layer thinning in OCT images of tamoxifen-treated mice. qRT-PCR revealed, in the tamoxifen-treated group, less upregulation of antioxidant and complement factor 3 mRNAs, and less reduction in the rhodopsin and short-wave cone opsin mRNAs. Furthermore, ERG results demonstrated preservation of photoreceptor function for the tamoxifen-treated group. Cone function was better protected than rods. These results indicate that tamoxifen provided structural and functional protection to photoreceptors against NaIO3. RPE cells were not protected. These neuroprotective effects suggest that estrogen-receptor modulation may be retina-protective. The fact that cones are particularly protected is intriguing given their importance for human visual function and their survival until the late stages of retinitis pigmentosa. Further investigation of this protective pathway could lead to new photoreceptor-protective therapeutics.
摘要：
因为选择性雌激素受体调节剂他莫昔芬在视网膜变性的光损伤和rd10模型中显示出视网膜保护作用,这项研究的目的是测试他莫昔芬在视网膜色素上皮(RPE)毒性似乎是主要损害的模型:碘酸钠(NaIO3)模型中是否具有视网膜保护作用.C57Bl/6J小鼠口服他莫昔芬（在饮食中）或缺乏他莫昔芬的相同饮食，然后腹膜内注射25mg/kg的NaIO3。一周后使用光学相干断层扫描(OCT)对小鼠成像。使用具有定制宏的ImageJ来测量OCT图像中的视网膜厚度。使用视网膜电图(ERG)测量注射后一周的视网膜功能。安乐死后,进行定量实时PCR(qRT-PCR)。他莫昔芬给药部分保护了光感受器。在他莫昔芬处理的小鼠的OCT图像中存在较少的光感受器层变薄。qRT-PCR显示，在他莫昔芬治疗组中，抗氧化剂和补体因子3mRNA的上调较少，视紫红质和短波视锥视蛋白mRNA的减少。此外，ERG结果证明了他莫昔芬治疗组的光感受器功能的保留。锥体功能比棒得到更好的保护。这些结果表明他莫昔芬为光感受器提供了针对NaIO3的结构和功能保护。RPE细胞不受保护。这些神经保护作用表明雌激素受体调节可能是视网膜保护作用。视锥受到特别保护的事实是有趣的，因为它们对人类视觉功能的重要性和它们的生存直到色素性视网膜炎的晚期阶段。对这种保护性途径的进一步研究可能会导致新的光感受器保护性疗法。
