New therapies against blindness possible with €22 million

Blindness can arise in various ways. In young individuals, hereditary retinal conditions are the primary cause, while age-related macular degeneration is the leading cause in the elderly. The Ministry of OCW is investing €22 million in the Lifelong Vision project, where researchers will develop new therapies that can be applied to different forms of blindness.

Gene editing with CRISPR/Cas

An essential component of the project is gene therapy. When a gene defect leads to blindness, doctors can already introduce an entirely new gene. They inject it beneath the retina in the eye, hoping it reaches the correct cells and induces those cells to produce healthy proteins again. "Unfortunately, this method doesn't work very well yet," says Professor of Epidemiology and Genetics of Eye Diseases Caroline Klaver from Radboudumc. "Many genes are not suitable for this because they are too large. Therefore, we aim to execute the repair much more precisely using gene editing. In this process, we only rewrite the defect in the gene, rather than replacing the entire gene." Camiel Boon, Professor of Ophthalmology and Clinical Ophthalmogenetics at Amsterdam UMC, adds, "In the laboratories of Amsterdam UMC, we will develop gene editing, also known as CRISPR/Cas, among other things. In the research group of Arthur Bergen, Professor of Genetic Eye Diseases, we are developing new disease models to optimally test these new treatments. Additionally, with the group led by Professor of AI and Health Clarisa Sánchez, we are using artificial intelligence to investigate who is most suitable for these innovative treatments. This ensures that the right patient receives the right treatment at the right time."

Natural abilities of zebrafish

Additionally, the researchers are exploring methods to protect cells in the eye. The reasons why a cell in the eye with a genetic defect dies have already been extensively mapped out. This provides clues on how to keep cells alive, for example, with a special cocktail of proteins that aid the cells in this process. Moreover, the strategy of zebrafish is highly intriguing: they can repair their retina on their own, something humans cannot do. The researchers aim to learn from how zebrafish achieve this and investigate whether it can be introduced in humans. Furthermore, the researchers will develop cell therapy. "The retina is brain tissue. It is a complex structure with up to ten different layers, in which nerve cells all interact with each other," explains Klaver. "Previously, we attempted to restore damaged retinas by injecting stem cells, but that didn't work well. Now, we will explore whether we can create a retina with a bio-printer, which layers the various cell types on top of each other. We will also investigate how this printed retina can integrate with the vascular layer. This is tremendously novel and exciting research."

The Lifelong Vision project involves eight research institutions. Principal Investigators of Amsterdam UMC include Camiel Boon, Arthur Bergen (Amsterdam UMC), and Clarisa Sánchez (UvA/Amsterdam UMC). Caroline Klaver of Radboudumc leads the project. Other principal investigators include Rob Collin and Ronald Roepman (Radboudumc).