The Crumbs homolog 1 () 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 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, 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 -mutation-associated retinal degenerations and suggest that antimicrobial agents have the potential to treat this devastating blinding disease.

中文翻译：

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CRB1相关的视网膜变性依赖于肠道细菌的移位

Crumbs 同源物 1 () 基因与视网膜变性有关，最常见的是莱伯先天性黑蒙 (LCA) 和色素性视网膜炎 (RP)。在这里，我们证明携带 Rd8 突变的小鼠视网膜的特征是病灶内细菌的存在。虽然正常的 CRB1 表达在视网膜色素上皮和结肠肠细胞的顶端连接复合体中丰富，但突变抑制了其在这两个部位的表达。 Rd8小鼠的外血视网膜屏障和结肠肠上皮屏障随之受损，导致肠道细菌从下消化道（GI）转移到视网膜，导致继发性视网膜变性。全身清除细菌或在结肠中重新引入正常的 Crb1 表达可以挽救 Rd8 突变相关的视网膜变性，但不会逆转视网膜屏障的破坏。我们的数据阐明了与突变相关的视网膜变性的发病机制，并表明抗菌药物有可能治疗这种毁灭性的致盲疾病。