中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (7): 1596-1603.doi: 10.4103/1673-5374.330622

• 原著:视神经损伤修复保护与再生 • 上一篇    下一篇

叶黄素延缓视网膜色素变性模型小鼠光感受器的变性

  

  • 出版日期:2022-07-15 发布日期:2022-01-18
  • 基金资助:
    爱尔眼科医院集团项目(AF2019001,AF2019002);国家自然科学基金项目(82074169);广州市脑科学与类脑智能技术重点项目(20200730009);广东省脑病治疗关键技术资助项目(2018B030332001);广东省自然科学基金项目(2021A1515012473);广东省中医药管理局项目(20202045)

Lutein delays photoreceptor degeneration in a mouse model of retinitis pigmentosa

Hui-Jun Zhang1, 2, Xiao-Bin Liu3, Xiong-Min Chen3, Qi-Hang Kong1, Yu-Sang Liu3, Kwok-Fai So3, 5, 6, 7, Jian-Su Chen1, 4, 5, Ying Xu3, 5, 6, 7, *, Xue-Song Mi1, 5, *, Shi-Bo Tang4, 5, *   

  1. 1Department of Ophthalmology, the First Affiliated Hospital of Jinan University, Guangzhou, Guangdong Province, China; 2Department of Ophthalmology, Guangzhou Panyu Central Hospital, Guangzhou, Guangdong Province, China; 3Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou, Guangdong Province, China; 4Laboratory of Retinal Cell Biology, Aier Eye Institute, Changsha, Hunan Province, China; 5Aier Academician Station, Changsha, Hunan Province, China; 6Key Laboratory of CNS Regeneration (Jinan University), Ministry of Education, Guangzhou, Guangdong Province, China; 7Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province, China
  • Online:2022-07-15 Published:2022-01-18
  • Contact: Ying Xu, PhD, xuying@jnu.edu.cn; Xue-Song Mi, MD, PhD, mxsong@163.com; Shi-Bo Tang, MD, PhD, tangshibo@vip.163.com.
  • Supported by:
    The study was supported by Aier Eye Hospital Group, Nos. AF2019001 and AF2019002 (to SBT, KFS, YX and XSM); the National Natural Science Foundation of China, No. 82074169 (to XSM); Guangzhou Key Projects of Brain Science and Brain-Like Intelligence Technology of China, No. 20200730009 (to YX); Guangdong Grant Key Technologies for Treatment of Brain Disorders, China, No. 2018B030332001 (to YX); Natural Science Foundation of Guangdong Province of China, No. 2021A1515012473 (to XSM) and Project of Administration of Traditional Chinese Medicine of Guangdong Province, No. 20202045 (to XSM).

摘要:

视网膜色素变性是一种以光感受器变性为特征的视网膜疾病,一般认为目前尚无有效的治疗方法。叶黄素联合其他抗氧化剂具有保护退化视网膜的潜力,但单独叶黄素对视网膜色素变性的作用人们仍不清楚。实验给予出生后第17至25天(当视杆细胞凋亡达到峰值时的时间)视网膜色素变性感光细胞变性模型Pde6b rd10小鼠灌胃叶黄素。结果发现,与溶剂干预的对照Pde6b rd10小鼠相比,叶黄素能显著促进光感受器的存活,且最佳保护剂量为200 mg/kg。进一步以这个剂量干预Pde6b rd10小鼠后发现,在结构上,叶黄素增加了Pde6b rd10小鼠的视杆细胞中视紫质的表达和视锥细胞中的视蛋白表达,提高了感光细胞的存活率;在功能上,叶黄素改善了Pde6b rd10小鼠的视觉行为、视敏度以及视网膜电流图反应;在机制上,叶黄素通过降低Müller胶质细胞中神经胶质纤维酸性蛋白的表达,抑制了视网膜中的反应性胶质增生,从而达到抗炎作用。因此,我们的结果证明了叶黄素可通过减少视网膜 Müller神经胶质增生以及抗炎作用延缓了视网膜色素变性中光感受器的退化。实验于2018年12月17日经暨南大学实验动物伦理委员会批准(批准号LACUC-20181217-02)。

https://orcid.org/0000-0003-4039-4246 (Kwok-Fai So); https://orcid.org/0000-0001-6703-9573 (Jian-Su Chen); https://orcid.org/0000-0002-7503-3996 (Hui-Jun Zhang); https://orcid.org/0000-0002-9987-2057 (Ying Xu); https://orcid.org/0000-0001-9146-1715 (Xue-Song Mi); https://orcid.org/0000-0003-2737-6780 (Shi-Bo Tang)

关键词: 视网膜色素变性, 光感受器, 抗炎, Pde6b rd10小鼠, 反应性胶质增生, 视网膜编变性, 叶黄素, 胶质纤维酸性蛋白, 小胶质细胞

Abstract: Retinitis pigmentosa is a retinal disease characterized by photoreceptor degeneration. There is currently no effective treatment for retinitis pigmentosa. Although a mixture of lutein and other antioxidant agents has shown promising effects in protecting the retina from degeneration, the role of lutein alone remains unclear. In this study, we administered intragastric lutein to Pde6brd10 model mice, which display degeneration of retinal photoreceptors, on postnatal days 17 (P17) to P25, when rod apoptosis reaches peak. Lutein at the optimal protective dose of 200 mg/kg promoted the survival of photoreceptors compared with vehicle control. Lutein increased rhodopsin expression in rod cells and opsin expression in cone cells, in line with an increased survival rate of photoreceptors. Functionally, lutein improved visual behavior, visual acuity, and retinal electroretinogram responses in Pde6brd10 mice. Mechanistically, lutein reduced the expression of glial fibrillary acidic protein in Müller glial cells. The results of this study confirm the ability of lutein to postpone photoreceptor degeneration by reducing reactive gliosis of Müller cells in the retina and exerting anti-inflammatory effects. This study was approved by the Laboratory Animal Ethics Committee of Jinan University (approval No. LACUC-20181217-02) on December 17, 2018.

Key words: anti-inflammation, glial fibrillary acidic protein, lutein, microglia, Pde6brd10 (rd10) mouse, photoreceptor, reactive gliosis, retinal degeneration, retinal disease, retinitis pigmentosa