Mutations in a protein called CRB1 (Crumbs homolog 1) can cause retinal degeneration, specifically Leber congenital amaurosis (LCA) and retinitis pigmentosa (RP). In our eyes,the blood-retina barrier acts as a "brick wall" that prevents potentially dangerous factors in our blood like bacteria from entering the eye. These researchers showed that in the eye, CRB1 protein acts as "mortar" in the brick wall, closing gaps between the cells that form the blood-retina barrier ensure nothing harmful from the blood supply can leak into the eye.
Previously, it was thought that the CRB1 protein was present only in cells of the eye and brain. In this study, researchers looked more carefully at other organs in the mouse and found that CRB1 is also found in the cells that line the intestines. The cells lining the intestines also act like a brick wall, preventing harmful bacteria from invading the rest of the body. CRB1 plays the same role as "mortar" in this cell barrier closing gaps between cells so that bacteria cannot leak through.
These researchers found that in mice where CRB1 was mutated and not functioning properly, both the intestinal walls and the blood-retina barrier became leaky. This allowed intestinal bacteria to leak out of the intestines and into the blood supply, and then leak into the retina. Bacteria in the retina increase inflammation, which causes additional damage to retinal cells and enhances retinal degeneration and vision loss. The researchers showed that reducing the amount of gut bacteria decreased the amount of bacteria in the retina, which decreased inflammation and improved retinal health.
What this means for Usher syndrome: These researchers showed how reducing inflammation improved the health of the retina, even when CRB1 was still mutated. Inflammation can occur in the retina during most types of retinal degeneration, including Usher syndrome, and this work shows that reducing inflammation can be a widely applied strategy to reduce retinal damage.
