A loss of night vision, a narrowing visual field (“tunnel” vision), then difficulty in distinguishing colors or flickering: these are the main symptoms that appear, generally between the ages of 10 and 20, in people with retinitis pigmentosa. In almost half of the cases, this genetic disease is hereditary, that is to say transmitted by the parents. In the other half of the cases, it is due to a mutation occurring in one of the fifty genes identified and involved in its appearance.
“Progressively affecting vision, retinitis pigmentosa can eventually lead to blindness,” explains Corinne Kostic, head of the “Retinal disorder research” group at the Eye Sciences Research Center of the Jules-Gonin Ophthalmic Hospital. (University Department of Ophthalmology of the University of Lausanne). The degeneration of photosensitive cells or photoreceptors (which capture light and convert it into a nerve signal) in retinitis pigmentosa 28 (one of the subtypes of the disease) has until now been poorly understood and does not benefit from any treatment.”
A collapsing structure
But to understand the disease, we must first know how these photoreceptors are made. These retinal cells contain a stack of discs bearing light-sensitive pigments. There, a connecting cilia acts as a support structure for all this machinery essential to the functioning of the cell. In these eyelashes, proteins act like a zipper to ensure the maintenance of the elements. “But mutations in the genes for these proteins can cause the structure to collapse, which leads to degeneration and then cell death,” explains Prof. Paul Guichard, researcher in the Department of Molecular and Cellular Biology of the UNIGE Faculty of Sciences and co-author of a recent study shedding new light on the functioning of the connecting cilia in retinitis pigmentosa type 281.
This work was made possible thanks to “super-resolution” imaging, expansion microscopy, developed in 2015 at the Massachusetts Institute of Technology (United States) and perfected by the UNIGE team. “This advanced technology has allowed us to better understand the role of proteins in maintaining the structure of retinal cells,” adds the researcher. The next step will be to duplicate in humans this work carried out for the moment only on mice.
Towards a potential treatment?
Understanding the mechanisms of retinitis pigmentosa opens the way to many avenues of research in an attempt to develop a treatment. In collaboration with the laboratory of Prof. Paul Guichard and Dr Virginie Hamel (UNIGE), the teams of Prof. Yvan Arsenijevic and Dr. Corinne Kostic from the Jules-Gonin Ophthalmic Hospital are now trying to replace the mutated gene with a healthy gene, in order to restore protein function and avoid the collapse of the cellular structure, or even the cell structure. to fix. “This is called replacement gene therapy,” explains Dr. Kostic. This is very promising, but we are at an experimental stage and many questions still remain unanswered.
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1. Mercey O, Kostic C, Bertiaux E, et al. The connecting cilium inner scaffold provides a structural foundation that protects against retinal degeneration. PLoS Biol. 2022 Jun 16;20(6):e3001649.