小柯机器人

中山大学魏来、张峰、魏泓及伦敦大学Richard RW Lee研究团队发现，CRB1相关的视网膜退行性疾病依赖于来自肠道的细菌易位。2024年2月26日出版的《细胞》杂志发表了这项成果。

课题组人员证明了携带Crb1 Rd8突变的小鼠视网膜存在斑块内细菌。虽然正常的CRB1在视网膜色素上皮和结肠肠细胞的顶端连接复合体中富集表达，但Crb1突变抑制了这两个部位的表达Rd8小鼠外周血视网膜屏障和结肠肠上皮屏障随之受损，导致肠道细菌从下胃肠道(GI)转移到视网膜，导致继发性视网膜变性。

无论是系统地消灭细菌，还是重新引入正常Crb1表达，都可以挽救Rd8突变相关的视网膜变性，而不会逆转视网膜屏障的破坏。他们的数据阐明了Crb1突变相关视网膜变性的发病机制，并表明抗菌药物有潜力治疗这种毁灭性的致盲疾病。

研究人员表示，CRB1基因与视网膜退行性疾病有关，最常见的是先天性黑内障(LCA)和色素性视网膜炎(RP)。

附：英文原文

Title: CRB1-associated retinal degeneration is dependent on bacterial translocation from the gut

Author: Shanzhen Peng, Jing Jing Li, Wanying Song, Ye Li, Lei Zeng, Qiaoxing Liang, Xiaofeng Wen, Haitao Shang, Keli Liu, Peiyao Peng, Wei Xue, Bin Zou, Liu Yang, Juanran Liang, Zhihui Zhang, Shixin Guo, Tingting Chen, Wenxuan Li, Ming Jin, Xiang-Bin Xing, Pengxia Wan, Chunqiao Liu, Haotian Lin, Hong Wei, Richard W.J. Lee, Feng Zhang, Lai Wei

Issue&Volume: 2024-02-26

Abstract: The Crumbs homolog 1 (CRB1) gene is associated with retinal degeneration, most commonly Leber congenital amaurosis(LCA) and retinitis pigmentosa (RP). Here, we demonstrate that murine retinas bearingthe Rd8 mutation of Crb1 are characterized by the presence of intralesional bacteria. While normal CRB1 expressionwas enriched in the apical junctional complexes of retinal pigment epithelium andcolonic enterocytes, Crb1 mutations dampened its expression at both sites. Consequent impairment of the outerblood retinal barrier and colonic intestinal epithelial barrier in Rd8 mice led tothe translocation of intestinal bacteria from the lower gastrointestinal (GI) tractto the retina, resulting in secondary retinal degeneration. Either the depletion ofbacteria systemically or the reintroduction of normal Crb1 expression colonicallyrescued Rd8-mutation-associated retinal degeneration without reversing the retinalbarrier breach. Our data elucidate the pathogenesis of Crb1-mutation-associated retinal degenerations and suggest that antimicrobial agents havethe potential to treat this devastating blinding disease.

DOI: 10.1016/j.cell.2024.01.040

Source: https://www.cell.com/cell/abstract/S0092-8674(24)00108-9