Sight loss in certain inherited eye illnesses may be caused by gut bacteria and could be treated with antimicrobials, according to a new study in mice conducted by a UCL and Moorfields researcher. The multinational study discovered gut bacteria within the damaged parts of the eye in eyes with sight loss caused by a specific genetic mutation, which is known to cause eye illnesses that lead to blindness.
The authors of the new report, published in Cell and co-led by Chinese experts, claim their findings imply that the genetic mutation may relax the body’s defenses, allowing hazardous bacteria to enter the eye and cause blindness. The gut contains trillions of microorganisms, many of which are essential for good 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.
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.
Professor Richard Lee
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 animal models, the researchers determined that the CRB1 gene is essential for maintaining the integrity of the lower gastrointestinal tract, which is the first time this has been shown. It combats infections and dangerous germs by controlling the flow of nutrients between the gut and the body.
The scientists discovered that when the gene has a specific mutation that dampens its expression (reduces its function), these barriers in both the retina and the gut can be crossed, allowing bacteria from the gut to migrate through the body and into the eye, resulting in retinal lesions that cause vision 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.”
