Who cleans up ‘the mess’ from the cones?


New research on the cause of blindness due to Usher syndrome

A research team led by Dr. Ronald Roepman (www.roepmanlab.com) is conducting research at Radboudumc, Netherlands, to investigate the underlying cause of vision loss in Usher syndrome. In this study, titled “Harnessing Autophagy to Combat Macular Degeneration,” they aim to gain more clarity on the death of cone cells in the retina. In a healthy eye, waste products in the retina are “cleaned up,” but in retinal diseases like Usher syndrome, this process is insufficient. The cones ultimately die because waste accumulates in harmful quantities within these cells. Thanks to the efforts of the participants in ‘Nederland wandelt voor Usher’ (Event Walks for Usher), Stichting Ushersyndroom (the Dutch Usher Syndrome Foundation) can finance a significant portion of this important research.

Crucial discovery
Hereditary blindness is a profound condition that seriously affects the lives of many patients. Researchers have been searching for effective treatments for some time, but the question of why waste products in the retina are not cleared in hereditary retinal diseases has remained unknown until now. Dr. Ronald Roepman, who collaborates in this promising project with Dr. Erik de Vrieze and Dr. Erwin van Wyk, recently made a crucial discovery that may provide an answer to this question. This could be a significant step toward a solution. Dr. Ronald Roepman says, “If you understand why the cones don’t clean up the waste, then you might be able to help them clean it up, perhaps with medication.”

The research focuses on understanding the mechanism of ‘autophagy’ in cone cells. Autophagy is a biological process in which certain components of a cell, such as damaged proteins or foreign particles, are broken down. Recent research data suggest that dysregulation of this process is a significant cause of cone cell death, leading to progressive vision loss in hereditary retinal disorders.

Death due to self-waste
An Usher gene contains instructions for producing a protein that keeps the light-sensitive cells in the retina – the rods and cones – healthy. Errors in this gene can lead to the protein’s malfunction and disrupt the processes. Cones produce substantial amounts of waste products, which are normally cleared through the autophagy process. If the Usher proteins are absent or not functioning properly, the cones cannot dispose of their waste products and essentially drown in their own ‘mess.’ The researchers aim to determine how the genetic defect is responsible for the malfunctioning autophagy.

Zebrafish and retinal organoids
The research team uses zebrafish as a model organism in the laboratory due to the striking similarities between their eyes and those of humans. They will compare healthy cone cells with cone cells displaying disrupted autophagy using zebrafish. Additionally, the research team will use retinal organoids, small retinas grown in the laboratory using cells from both Usher syndrome patients and people with healthy eyes. These organoids provide a valuable platform to study the autophagy mechanism in healthy and diseased cells.

Hope for finding a safe and effective treatment
Once the autophagy mechanism is understood, the research team will search for substances that can stimulate the autophagy process, thereby reducing or preventing cone cell death. With the help of a database containing thousands of substances known to stimulate or inhibit proteins, they hope to find a safe and effective treatment.

Also, for other hereditary retinal diseases
This promising research will not only contribute to detailed knowledge about autophagy and cone cell death but also offer possibilities for further treatment development. If the results of this research prove successful, this project could slow down vision deterioration and have a significant impact on the quality of life for Usher syndrome patients. Dr. Roepman says, “It could offer a solution not only for Usher syndrome but also for patients with Retinitis Pigmentosa (RP), Macular Degeneration (MD), and all other forms of hereditary retinal diseases.”

The current project has a duration of three years. Stichting Ushersyndroom plays a significant role in the research by financing a large portion of the required budget. We are not the sole financiers of this research. Thanks to the L.S.B.S. (National Foundation for the Blind and Visually Impaired) and the donors of the Oogfonds (Dutch Eye Foundation), they are co-funders for this project, providing a valuable financial contribution to make this promising research possible.

The voucher was presented during the festive day at the Railway Museum in Utrecht on Global Usher Awareness Day 2023.

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