Genetics Eye diseases long thought to be purely genetic might be caused in part by bacteria that escape the gut and travel to the retina (Feb 2024, mice) CRB1-associated retinal degeneration is dependent on bacterial translocation from the gut

Michael Harrop

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https://www.nature.com/articles/d41586-024-00562-2
https://www.cell.com/cell/abstract/S0092-8674(24)00108-9

Highlights​

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