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

[Mary Wilson]

Published: February 26, 2024

DOI: https://doi.org/10.1016/j.cell.2024.01.040​

Shanzhen Peng [SUP]1[/SUP],Jing Jing Li [SUP]12[/SUP],Wanying Song [SUP]12[/SUP],Richard W.J. Lee [SUP]13[/SUP],Feng Zhang [SUP]13[/SUP],Lai Wei [SUP]13[/SUP][SUP], [/SUP][SUP]14 [/SUP]Show all authors​

Highlights

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  CRB1 is critical to epithelial barrier integrity in both the retina and colon
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  Crb1 mutations permit bacterial translocation from the gut to the eye
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  Crb1-associated retinal degeneration is dependent on this bacterial translocation
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  Germ-free conditions and antibiotics rescue Crb1-associated retinal degeneration

Summary

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.

$$ https://www.cell.com/cell/abstract/S0092-8674(24)00108-9
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[Mary Wilson]

The surprising link between gut bacteria and devastating eye diseases - Nature

26 February 2024​
By Saima Sidik​

Eye diseases long thought to be purely genetic might be caused in part by bacteria that escape the gut and travel to the retina, research suggests[SUP]1[/SUP].

Eyes are typically thought to be protected by a layer of tissue that bacteria can’t penetrate, so the results are “unexpected”, says Martin Kriegel, a microbiome researcher at the University of Münster in Germany, who was not involved in the work. “It’s going to be a big paradigm shift,” he adds.

The study was published on 26 February in Cell.

​Crumbling dogma
Inherited retinal diseases, such as retinitis pigmentosa, affect about 5.5 million people worldwide. Mutations in the gene Crumbs homolog 1 (CRB1) are a leading cause of these conditions, some of which cause blindness. Previous work[SUP]2[/SUP] suggested that bacteria are not as rare in the eyes as ophthalmologists had previously thought, leading the study’s authors to wonder whether bacteria cause retinal disease, says co-author Richard Lee, an ophthalmologist then at the University College London.

CRB1 mutations weaken linkages between cells lining the colon in addition to their long-observed role in weakening the protective barrier around the eye, Lee and his colleagues found.​ ...

https://www.nature.com/articles/d41586-024-00562-2
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