Subcutaneous delivery of tauroursodeoxycholic acid rescues the cone photoreceptors in degenerative retina: A promising therapeutic molecule for retinopathy
Subcutaneous delivery of tauroursodeoxycholic acid rescues the cone photoreceptors in degenerative retina: A promising therapeutic molecule for retinopathy
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皮下注射牛磺熊去氧胆酸可挽救退行性视网膜中的视锥细胞：一种有前途的视网膜病治疗分子
DOI：
10.1016/j.biopha.2019.109021
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发表时间：
2019-09-01
影响因子：
7.5
通讯作者：
Zhang, Jianbin
中科院分区：
文献类型：
--
作者：
Tao, Ye;Dong, Xin;Zhang, Jianbin
遗传性视网膜变性 (RD) 包括一组异质性视网膜病变，是导致失明的主要原因之一。牛磺熊去氧胆酸 (TUDCA) 是牛磺酸缀合物亲水性胆汁酸，对一系列与氧化应激相关的神经退行性疾病具有深远的保护作用。本研究试图通过视网膜电图（ERG）检查、行为测试、形态学分析和免疫化学测定来评估 TUDCA 对药理学诱导的 RD 动物模型的影响。腹腔注射N-甲基N-亚硝基脲（MNU）可诱导小鼠视网膜发生大量光感受器变性。皮下注射 TUDCA 可有效抑制 MNU 给药小鼠的光感受器损失和视力障碍。在 TUDCA 处理小鼠的视网膜平板上，视锥光感受器得到了有效的保存。此外，多电极阵列（MEA）用于检测视网膜内部回路内视网膜神经节细胞的放电活动。 TUDCA治疗可以抑制自发放电反应，增强光诱导放电反应，并保留退变视网膜中ON-OFF信号通路的基本配置。我们的 MEA 测定提供了一个评估药理学化合物对视网膜可塑性的效力的例子。 TUDCA 通过调节细胞凋亡和减轻退行性视网膜中的氧化应激来提供这些保护作用。总之，TUDCA疗法可以改善光感受器变性并纠正视觉信号传输的异常。这些发现表明 TUDCA 可能作为治疗这些伴有进行性光感受器变性的视网膜病变的潜在药物。
Inherited retinal degeneration (RD) comprises a heterogeneous group of retinopathies that rank among the main causes of blindness. Tauroursodeoxycholic acid (TUDCA) is taurine conjugate hydrophilic bile acid that demonstrates profound protective effects against a series of neurodegenerative diseases related to oxidative stress. This study sought to evaluate the TUDCA induced effects of on a pharmacologically induced RD animal model by electroretinogram (ERG) examination, behavior tests, morphological analysis and immunochemistry assay. Massive photoreceptor degeneration in mice retina was induced by an intraperitoneal administration of N-methyl N-nitrosourea(MNU). Subcutaneous delivery of TUDCA inhibits effectively the photoreceptor loss and visual impairments in the MNU administered mice. In the retinal flat-mounts of TUDCA treated mice, the cone photoreceptors were efficiently preserved. Furthermore, the multi-electrodes array (MEA) was used to detect the firing activities of retinal ganglion cells within the inner retinal circuits. TUDCA therapy could restrain the spontaneous firing response, enhance the light induced firing response, and preserve the basic configurations of ON-OFF signal pathway in degenerative retinas. Our MEA assay provided an example to evaluate the potency of pharmacological compounds on retinal plasticity. TUDCA affords these protective effects by modulating apoptosis and alleviating oxidative stress in the degenerative retina. In conclusion, TUDCA therapy can ameliorate the photoreceptor degeneration and rectify the abnormities in visual signal transmission. These findings suggest that TUDCA might act as a potential medication for these retinopathies with progressive photoreceptor degeneration.