Retinitis pigmentosa is the most common hereditary retinal disease in humans, with a prevalence of one in every 4,000 people worldwide. Scientists from the University of Geneva (UNIGE), in collaboration with the University of Lausanne (UNIL), report they have identified the role played by a molecular zipper formed by four proteins. They observed that the absence of this zipper leads to cell death in retinal cells. Their findings in mice may lead to the development of therapeutic treatments and strategies for retinitis pigmentosa.

The new study is published in the journal PLOS Biology in a paper titled, “The connecting cilium inner scaffold provides a structural foundation that protects against retinal degeneration.”

“Inherited retinal degeneration due to loss of photoreceptor cells is a leading cause of human blindness,” wrote the researchers. “These cells possess a photosensitive outer segment linked to the cell body through the connecting cilium (CC). While structural defects of the CC have been associated with retinal degeneration, its nanoscale molecular composition, assembly, and function are barely known. Here, using expansion microscopy and electron microscopy, we reveal the molecular architecture of the CC and demonstrate that microtubules are linked together by a CC inner scaffold containing POC5, CENTRIN, and FAM161A.” The first symptoms usually appear between the ages of 10 and 20 with a loss of night vision. Thereafter, the visual field narrows into a “tunnel vision” to finally lead to blindness around the age of 40. This disease is characterized by a degeneration of light-sensitive cells, the photoreceptors.

“In the centriole, these proteins ensure the cohesion of the different microtubules by acting like a zipper. We wondered if they did not play the same role in the tubular structures of the connecting cilium,” said Virginie Hamel, PhD, co-group leader and senior lecturer, UNIGE, and last author of the study.

“In the absence of the mutation, we found that these proteins ensure, just as we had previously seen in centrioles, the cohesion between microtubules by forming a zipper that closes as development proceeds,” explained Olivier Mercey, a researcher in the department of molecular and cellular biology and first author of the study.

The researchers predict that by injecting the protein into patients suffering from certain types of retinitis pigmentosa, they 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.

The team is currently evaluating their approach in collaboration with their colleagues from UNIL and the Jules-Gonin Ophthalmic Hospital.

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