Summary: Researchers found a surprising connection between gut bacteria and inherited eye diseases, potentially opening new treatment avenues using antimicrobials. They discovered that a specific genetic mutation could weaken the body’s defenses, allowing gut bacteria to infiltrate the eye and cause sight loss.
The study focused on the CRB1 gene, crucial for maintaining the integrity of the eye’s and gut’s barriers. By treating affected mice with antimicrobials, the team successfully prevented blindness without repairing the damaged cellular barriers, suggesting a novel treatment strategy for CRB1-linked eye diseases.
Key Facts:
- The study identifies a link between gut bacteria and blindness in mice with a specific genetic mutation affecting the CRB1 gene.
- Antimicrobial treatment prevented sight loss in mice, indicating a potential new therapy for inherited eye diseases.
- This research could transform the treatment landscape for CRB1-associated eye conditions and possibly extend to other eye diseases.
Source: UCL
Sight loss in certain inherited eye diseases may be caused by gut bacteria, and is potentially treatable by antimicrobials, finds a new study in mice co-led by a UCL and Moorfields researcher.
The international study observed that in eyes with sight loss caused by a particular genetic mutation, known to cause eye diseases that lead to blindness, gut bacteria were found within the damaged areas of the eye.
The authors of the new paper, published in Cell and jointly led by researchers in China, say their findings suggest that the genetic mutation may relax the body’s defences, thus allowing harmful bacteria to reach the eye and cause blindness.
The gut contains trillions of bacteria, many of which are key to healthy digestion. However, they can also be potentially harmful.
The researchers were investigating the impact of the Crumbs homolog 1 (CBR1) gene, which is known to be expressed in the retina (the thin layer of cells at the back of the eye) and is crucial to building the blood-retina barrier to regulate what flows in and out of the eye.
The CRB1 gene is associated with inherited eye disease, most commonly forms of Leber congenital amaurosis (LCA) and retinitis pigmentosa (RP); the gene is the cause of 10% of LCA cases and 7% of RP cases worldwide.
Using mouse models, the research team discovered the CRB1 gene is key to controlling the integrity of the lower gastrointestinal tract, the first ever such observation. There, it combats pathogens and harmful bacteria by regulating what passes between the contents of the gut and the rest of the body.
The team found that when the gene has a particular mutation, dampening its expression (reducing its effect), these barriers in both the retina and the gut can be breached, enabling bacteria in the gut to move through the body and into the eye, leading to lesions in the retina that cause sight loss.
Crucially, treating these bacteria with antimicrobials, such as antibiotics, was able to prevent sight loss in the mice even though it did not rebuild the affected cell barriers in the eye.
Inherited eye diseases are the UK’s leading cause of blindness in working-age people. Onset of disease may vary from very early childhood to adulthood, but deterioration is irreversible and has lifelong implications. To date, the development of treatments has largely focused on gene therapies.
The findings of this study suggest that simply using antimicrobials might help prevent deterioration in CRB1-associated inherited eye diseases. Future work will investigate whether this applies in humans.
Co-lead author Professor Richard Lee (UCL Institute of Ophthalmology and Moorfields Eye Hospital NHS Foundation Trust) said: “We found an unexpected link between the gut and the eye, which might be the cause of blindness in some patients.
“Our findings could have huge implications for transforming treatment for CRB1-associated eye diseases. We hope to continue this research in clinical studies to confirm if this mechanism is indeed the cause of blindness in people, and whether treatments targeting bacteria could prevent blindness.
“Additionally, as we have revealed an entirely novel mechanism linking retinal degeneration to the gut, our findings may have implications for a broader spectrum of eye conditions, which we hope to continue to explore with further studies.”
The study was an international collaboration led by researchers from Zhongshan Ophthalmic Center, Sun Yat-sen University, China, working with UCL Institute of Ophthalmology and Moorfields Eye Hospital NHS Foundation Trust.
About this genetic, vision, and microbiome research news
Author: Chris Lane
Source: UCL
Contact: Chris Lane – UCL
Image: The image is credited to Neuroscience News
Original Research: Closed access.
“CRB1-associated retinal degeneration is dependent on bacterial translocation from the gut” by Richard Lee et al. Cell
Abstract
CRB1-associated retinal degeneration is dependent on bacterial translocation from the gut
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.
