Breakthrough research reveals gut-eye connection in vision loss

Inherited retinal degeneration (IRD) encompasses various disorders characterized by progressive loss of retinal photoreceptor cells, ultimately leading to vision loss and blindness. Among the numerous genetic factors implicated in IRD, mutations in the CRB1 gene stand out as significant contributors to severe forms of retinal degeneration, including retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA). Recent research has unveiled a novel mechanism linking CRB1 mutations to retinal degeneration through bacterial translocation from the gut to the eye, opening up promising therapeutic avenues.

The CRB1 gene encodes a transmembrane protein crucial for maintaining the integrity of epithelial barriers in both the retina and the colon. In the retina, CRB1 plays a vital role in the structure and function of photoreceptor cells and the blood-retinal barrier (BRB). Recent studies have shown that CRB1 is also expressed in colonic enterocytes, where it maintains the integrity of adherens junctions (AJ) and the colonic epithelial barrier. Mutations in CRB1 disrupt these barriers, creating a "leaky gut" and "leaky retina" phenomenon that allows gut bacteria to translocate to the retina.

This bacterial translocation triggers inflammatory responses and retinal damage in CRB1-mutated eyes. Research using the naturally occurring retinal degeneration 8 (Rd8) mouse model, which carries a nonsense mutation in CRB1, has demonstrated that retinal lesions contain bacterial species originating from the gut. These findings establish a clear connection between CRB1 mutations, barrier dysfunction, and retinal inflammation.

The therapeutic potential of targeting this bacterial translocation has been explored through both antibiotic treatment and gene therapy approaches. Systemic antibiotic treatment of newborn Rd8 mice effectively prevented retinal damage by reducing bacterial translocation. Similarly, gene therapy using adeno-associated virus (AAV) vectors to restore CRB1 expression in enterocytes improved intestinal barrier function and reduced retinal inflammation.

These findings suggest that combining antibacterial therapy with gene correction could offer a promising treatment strategy for CRB1-associated retinal degeneration. The research highlights the importance of considering both local retinal treatment and systemic approaches addressing gut barrier function.
The discovery of this gut-eye axis in CRB1-related retinal degeneration has broader implications for understanding other ocular diseases where gut microbiota may play a role. Future research should explore whether similar mechanisms operate in human patients with CRB1 mutations and investigate the potential for probiotics, prebiotics, or other microbiome-modulating therapies to complement traditional gene therapy approaches.

In conclusion, this research represents a significant advancement in our understanding of CRB1-associated retinal degeneration and offers new therapeutic directions that could potentially slow or prevent vision loss in these currently untreatable conditions.

Source:
Journal reference:

He, Z., et al. (2025). Unlocking therapeutic potential: antibacterial therapy for CRB1-associated retinal degeneration in Rd8 mice. Frontiers of Medicine. doi.org/10.1007/s11684-024-1112-4.

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