Department of Physiology, Basic Medical College, Zhengzhou University, Zhengzhou, 450001, China; Lab of Visual Cell Differentiation, Basic Medical College, Zhengzhou University, Zhengzhou, 450001, China.
Department of Orthopedic Surgery, Orthopedics Oncology Institute of Chinese PLA, Tangdu Hospital, Fourth Military Medical University, Xi'an, 710038, China.
Biomed Pharmacother. 2019 Sep;117:109021. doi: 10.1016/j.biopha.2019.109021. Epub 2019 Jul 4.
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.
遗传性视网膜变性（RD）是一组异质性的视网膜病变，是导致失明的主要原因之一。牛磺熊脱氧胆酸（TUDCA）是牛磺酸结合的亲水性胆汁酸，对一系列与氧化应激相关的神经退行性疾病具有显著的保护作用。本研究通过视网膜电图（ERG）检查、行为测试、形态分析和免疫化学分析，评估了 TUDCA 对药物诱导的 RD 动物模型的诱导作用。通过腹腔内给予 N-甲基-N-亚硝基脲（MNU）诱导小鼠视网膜内大量光感受器变性。TUDCA 的皮下给药能有效抑制 MNU 给药小鼠的光感受器丧失和视力损害。在 TUDCA 处理的小鼠视网膜扁平片中，视锥细胞得到有效保存。此外，多电极阵列（MEA）用于检测内视网膜回路中神经节细胞的放电活动。TUDCA 治疗可抑制自发放电反应，增强光诱导的放电反应，并保持变性视网膜中 ON-OFF 信号通路的基本结构。我们的 MEA 检测提供了一个评估视网膜可塑性的药理学化合物效力的范例。TUDCA 通过调节变性视网膜中的细胞凋亡和减轻氧化应激来发挥这些保护作用。总之，TUDCA 治疗可以改善光感受器变性，并纠正视觉信号传递中的异常。这些发现表明，TUDCA 可能作为一种具有进行性光感受器变性的视网膜病变的潜在药物。
