Research suggests that eye diseases that have long been thought to be purely hereditary may be caused in part by bacteria that escape the gut and spread to the retina1.
Martin Kriegel, a microbiome researcher at the University of Münster in Germany, who was not involved in the work, said that the eye is often thought to be protected by a layer of tissue that bacteria can't penetrate, so the results are "unexpected." "It's going to be a huge paradigm shift," he added.
The study was published Feb. 26 in the journal Cell.
Crumbling dogma.
Inherited retinal diseases, such as retinitis pigmentosa, affect about 5.5 million people worldwide. Mutations in the Crumbs homolog 1 (CRB1) gene are the leading causes of these diseases, some of which can lead to blindness. Previous study2 showed that bacteria were not as rare in the eye as ophthalmologists had previously thought, leading the study's authors to wonder if bacteria could cause retinal disease, said co-author, Richard Lee, an ophthalmologist at University College London at the time.
Lee and his colleagues found that CRB1 mutations weakened the connections between colon cells, in addition to the long-observed effect of weakening the protective barrier around the eye. This prompted Wei Lai, an ophthalmologist at Guangzhou Medical University in China, a co-author of the study, to produce CRB1 mutant mice with depleted bacterial levels. Unlike mice with typical gut microbiota, these mice showed no evidence of distortion of the retinal cell layer.
In addition, mice with antibiotic** mutants reduced damage to their eyes, suggesting that people with CRB1 mutations could benefit from antibiotics or anti-inflammatory drugs that reduce the effects of bacteria. "If this is a new mechanism that can be **, it will change the lives of many families," Lee said. ”。
Suppress your enthusiasm.
Jeremy Kay, a neurobiologist at Duke University in Durham, North Carolina, said that although the article presents a "cool idea," people with CRB1 mutations should keep their excitement in check. "I'm very worried that patients will read this and think they have a simple answer," he said, while in fact, a complex picture remains.
Of the types of mice used in the study, CRB1-related eye disease typically takes years to fully develop — well beyond the time frame of the study — leaving Kay uncertain whether the findings will translate to humans. What's more, "I don't believe they've proven that bacteria can really get into the eye widely and do anything," he said. If gut bacteria cause an eye infection, "you would think [the infection] is happening elsewhere as well," which has not been observed in people with CRB1 mutations.
"Translation has always been a big problem [for humans]," Lee said. ”。At the same time, Kriegel said, bacteria that transfer from the gut can preferentially infect certain other sites, and the reason scientists still don't know. Because bacteria are rare in the eye, small amounts of bacteria can have a huge impact.
"There's no harm in trying antibiotics on patients," Kay said. ”。But he also believes that CRB1 can cause harmful genetic changes to the eyes even in the absence of bacteria. So, while antibiotics may help with retinal damage, they "don't reverse or ** it".