According to a new mouse study, gut bacteria may contribute to vision loss in some eye diseases, which may be treated with antibiotics**.
Researchers from China and the United Kingdom have found bacteria with mutations in the Crumbs homolog 1 (CRB1) gene, the leading cause of hereditary eye diseases, in the gut of damaged areas of the eyes of mice.
Richard Lee, an ophthalmologist at University College London and senior author of the study, said: "We found an unexpected link between the gut and the eye, which may be the cause of blindness in some patients. ”。
Our findings may have tremendous implications for changing the approach to CRB1-related eye diseases. ”
This is an early study, and we don't know if the same mechanism occurs in humans with CRB1 mutations, which cause retinitis pigmentosa in 4% of cases, leading to decreased peripheral and night vision, and 10% of Leber congenital amaurosis and about a third of cases lead to complete blindness.
Among the eye diseases associated with CRB1, the visual impairment begins at a young age. The retina – the tissue at the back of our eye that converts wavelengths of light into signals that our brain interprets as vision – failed to form its thin layer of photoreceptor cells and became unusually thick.
After previous studies found that bacteria are unexpectedly common in the eye, the team wanted to know if the bacteria can cause retinal damage.
Most of our trillions of gut bacteria are beneficial, not harmful, and they play a vital role in overall health. But Lee and colleagues believe that the CRB1 mutation allows gut bacteria to enter the eye, causing vision loss.
The CRB1 protein encoded by this gene is thought to be found only in the brain and in the retinal pigment epithelium (RPE), the outer blood-retinal barrier that protects the eye. For the first time, researchers have discovered that the intestinal wall also expresses this protein.
The CRB1 protein is essential for maintaining the barrier between the gut and the rest of the body, as well as between RPE. The mutated CBR1 gene does not express enough CRB1 protein, resulting in the disruption of these two protective barriers.
The mutated mouse model had damage at both barriers, allowing gut bacteria to enter the retina through the bloodstream and cause damage. Antibiotics** reduce retinal damage and prevent vision loss.
When the researchers reintroduced normal CRB1 expression into the gut of CRB1 mutant mice, it did not reverse the barrier disruption, but the damage to the retina was reduced. CRB1 mutant mice with reduced bacterial numbers also did not show as much retinal damage.
"We hope to continue this research in clinical studies to confirm whether this mechanism is indeed the cause of blindness in humans, and whether targeting bacteria can prevent blindness," Lee said. ”。
This just suggests that there may be a link between eye diseases caused by mutations in the CRB1 gene. Nearly 100 genes affecting retinal photoreceptor cells cause retinitis pigmentosa, and mutations in at least 28 genes cause Leber congenital amaurosis.
Genes have shown promise in hereditary eye diseases and have been the main focus of the development of methods to date. Although in 2023, scientists have linked specific immune cells that migrate from the gut to the retina to the severity of glaucoma.
Their findings, the authors say, suggest that the gut and eye are connected in another way — that live bacteria can be transferred from a leaky gut to the retina. We don't yet fully understand the gut connection to eye health, but this could be another avenue to consider.
"As we reveal a novel mechanism linking retinal degeneration to the gut, our findings may have implications for a wider range of eye diseases, which we hope to continue to explore through further research," Lee said. ”
The study has been published in the journal Cell.