Sight loss in certain inherited eye diseases may be caused by gut bacteria, and is potentially treatable by antimicrobials, a new international study has found.
The study in mice observed gut bacteria in eyes with sight loss caused by a particular genetic mutation, known to cause eye diseases that lead to blindness.
The gut bacteria were found within the damaged areas of the eye.
The authors of the new paper, published in Cell, 1 said their findings suggest that the genetic mutation may relax the body’s defences, allowing harmful bacteria to reach the eye and cause blindness.
The researchers were investigating the impact of the Crumbs homolog 1 (CBR1) gene, which is known to be expressed in the retina 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.
LCA is characterised by poor vision at birth or in the first few months of life. The degree of vision loss can remain stable over time, or it can progressively deteriorate.2 RP results in progressive vision loss. Onset varies depending on the type of RP but more than three-quarters of individuals with RP will be symptomatic by the time they are 30 years old.3
CONTROLLING GASTROINTESTINAL INTEGRITY
Using mouse models, the research team discovered CRB1 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, the barriers in both the retina and the gut can be breached. This enables 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.
Co-lead author Professor Richard Lee (UCL Institute of Ophthalmology and Moorfields Eye Hospital NHS Foundation Trust) said the “unexpected link between the gut and the eye” 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.
References
- Peng, S., Li,J.J., Lee, R.W., et al., CRB1-associated retinal degeneration is dependent on bacterial translocation from the gut, Cell, 2024; Published online 26 Feb 2024. DOI: 10.1016/j. cell.2024.01.040.
- Centre for Eye Research Australia, Leber congenital amaurosis (LCA) and early-onset severe retinal dystrophy (EOSRD) (webpage). Available at: cera.org.au/conditions/ leber-congenital-amaurosis-lca-and-early-onset-severe-retinaldystrophy-eosrd [accessed 27 Feb 2024].
- O’Neal, T.B., Luther, E.E., Retinitis Pigmentosa. (webpage, updated 19 Feb 2023). In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available at: ncbi.nlm.nih. gov/books/NBK519518/ [accessed 27 Feb 2024]
