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 bearing the Rd8 mutation of Crb1 are characterized by the presence of intralesional bacteria. While normal CRB1 expression was enriched in the apical junctional complexes of retinal pigment epithelium and colonic enterocytes, Crb1 mutations dampened its expression at both sites. Consequent impairment of the outer blood retinal barrier and colonic intestinal epithelial barrier in Rd8 mice led to the translocation of intestinal bacteria from the lower gastrointestinal (GI) tract to the retina, resulting in secondary retinal degeneration. Either the depletion of bacteria systemically or the reintroduction of normal Crb1 expression colonically rescued Rd8-mutation-associated retinal degeneration without reversing the retinal barrier breach. Our data elucidate the pathogenesis of Crb1-mutation-associated retinal degenerations and suggest that antimicrobial agents have the potential to treat this devastating blinding disease.
摘要：
面包屑同源物1（CRB1）基因与视网膜变性有关，最常见的是Leber先天性黑蒙（LCA）和视网膜色素变性（RP）。这里,我们证明了带有Crb1的Rd8突变的鼠视网膜的特征在于存在病灶内细菌。而正常的CRB1表达在视网膜色素上皮和结肠肠上皮细胞的顶端连接复合物中富集，Crb1突变抑制了其在两个位点的表达。Rd8小鼠外血视网膜屏障和结肠肠上皮屏障的损伤导致肠道细菌从下胃肠道(GI)向视网膜的易位,导致继发性视网膜变性.细菌的全身性消耗或正常Crb1表达的重新引入均可在结肠上挽救Rd8突变相关的视网膜变性，而不会逆转视网膜屏障的破坏。我们的数据阐明了Crb1突变相关视网膜变性的发病机理，并表明抗微生物剂具有治疗这种破坏性致盲疾病的潜力。
