Scientists in Europe have discovered a molecular “zipper” mechanism that can lead to cell death in the genetic disease retinitis pigmentosa. The good news is that injecting certain proteins could slow down or prevent vision impairment from the disease.
Retinitis pigmentosa is a relatively common hereditary disease that affects the photoreceptors, cells in the eye that register light. As they degenerate, patients will start to lose their night vision and peripheral vision, and over decades can become partially or completely blind. Unfortunately, there are few treatment options.
Photoreceptor cells are tiny and complicated, making it difficult to tell exactly what’s going on in there as the disease progresses. So for the new study, the team used an emerging technique known as expansion microscopy to inflate cells without deforming them, allowing retinal tissue to be examined at a higher resolution than ever before.
The scientists focused on a component of the photoreceptors known as the connecting cilia, which links the outer, light-sensitive pigments of the cell to the machinery that converts that light into nerve signals. This connecting cilia has been implicated in retinitis pigmentosa, but what that role is has remained a mystery.
Using expansion microscopy, the team identified that four proteins drive a series of microtubules to stick together in a kind of “zipper” formation, which holds the cilia together. But when the gene that codes for one of these proteins, called FAM161A, has a particular mutation, those microtubules don’t zip up as tightly. Over time, they unravel and eventually collapse, which kills off the photoreceptors, causing the vision impairment associated with retinitis pigmentosa.
While this work is mostly foundational in improving our understanding of how the disease occurs, the team says that it could also inform new potential treatments to prevent cell death and vision impairment. One idea will be evaluated in follow-up work.
“By injecting the protein into patients suffering from certain types of retinitis pigmentosa, we can imagine that the molecular zipper could be restored to ensure the structural integrity of the microtubules of the connecting cilia, thus preventing the death of photoreceptor cells,” said Paul Guichard, co-author of the study.
The research was published in the journal PLOS Biology.
Source: Université de Genève
