'Everyone, young and old, should be able to keep his eyesight' Ten year of Research led by Caroline Klaver of Radboudumc

19 September 2024

This year, she secured an NWO Gravitation grant, one of the most prestigious scientific awards in the Netherlands. With this funding, she will conduct research on blindness over the next ten years. Caroline Klaver’s goal? ‘Everyone, young and old, should be able to keep his eyesight.’  

‘Yes, it is quite special that we have received this grant,’ confirms ophthalmologist and professor Caroline Klaver. But she quickly adds, ‘This is not just my work. This grant is meant for consortia. We are working with 28 researchers from nine institutions. A large part of them works here at Radboud university medical center, where we excel in blindness research.’ 

Klaver is the consortium leader of the Lifelong Vision project. The consortium receives 22 million euros, enough for ten years of research. Klaver says, ‘This is almost unheard of. Most grants are for a maximum of five years. With the Gravitation grant, we can do a lot, including high-risk research: work that we think has potential, but we are not sure if it will succeed.’ 

Lifelong Vision

Lifelong Vision focuses on two common retinal diseases that lead to blindness. First, the main cause of blindness in young people: monogenetic retinal diseases, such as Retinitis Pigmentosa and Usher syndrome. In people over 55, Age-related Macular Degeneration (AMD) is the most common. This affects the central part of the retina, necessary for reading and recognizing faces, causing vision to gradually decline. 

‘We know a lot about the causes of these conditions,’ Klaver explains. For AMD, lifestyle plays an important role, especially smoking and unhealthy eating. ‘Additionally, 34 different genes are involved in AMD, five of which are very important.’ She discovered the first of these 34 genes as a young researcher, basically by logical thinking: ‘It was a gene important in dementia, APOE. I thought: AMD is dementia of the eye, so maybe this gene is also involved. And it turned out to be true.’ 

Already during her training, she was captivated by lab research: ‘I studied eye abnormalities in patients after a heart transplant, under the guidance of ophthalmologist and professor Carel Hoyng, who has long been at Radboudumc. We discovered that the transplant sometimes causes a huge inflammatory reaction in the eye, which I found very special. With this kind of research, you can make a difference.’

Ophthalmologist and professor Caroline Klaver

The retina: the outpost of our brain 

The retina is a thin layer that lines the inside of the back of our eyes. It is very sensitive to light and contains millions of cells: cones and rods. These so-called photoreceptors capture the light entering the eye and convert it into electrical signals. These signals then travel through several other cell layers and the optic nerve to the brain, which then turns them into the image we see. Caroline Klaver says, ‘The retina is the outpost of our brain, and unlike our brain, it can be imaged well. That makes our research incredibly interesting for other organs as well.’ 

Rewrite the error in the gene 

An important treatment for both monogenetic retinal diseases and AMD is gene therapy, Klaver explains. This involves introducing a version of a healthy gene into the eye, which takes over the function of a defective gene. ‘The eye was the first organ where gene therapy was successfully applied, but we now see that the positive effects do not last in the long term.’ Therefore, Lifelong Vision aims to carry out the repair much more precisely with the help of the Gravitation grant, not replacing the entire gene but only the faulty part. ‘At Radboudumc, we are very good at this. Researchers Rob Collin and Carel Hoyng are particularly involved in developing this and the next steps towards the clinic.’ 

Envious of zebrafish? 

This gene therapy can only be applied if the retinal tissue is still intact, and the cells are still repairable. If not, the therapy is useless. Caroline Klaver says, ‘That's why we also want to understand the disease mechanism and why a cell dies. This provides leads to keep cells alive, for example, with a special cocktail of proteins that help the cells. Geneticist Ronald Roepman will be doing this. In particular, we are looking at zebrafish. They have something we really want to have: they can repair their retina. Together with researcher Erwin van Wijk, we want to try to translate this to humans.’ 

Retina from a bio-printer 

The retina consists of ten layers on top of each other that communicate with each other. But what if there is nothing left? Then you need a new retina. Making one is very complicated, says Klaver: ‘We want to know if we can make a retina with a bio-printer, which may be able to layer the different cell layers on top of each other. And we are investigating how that printed retina can connect with the choroid. This is truly high-risk research: I don't know how far we will get in ten years.’ 

The next step is taken by researcher Zohreh Hosseinzadeh. She develops models to test whether the therapies work in the lab. Then comes an even bigger question: can we predict who needs which treatment? To do this, Klaver will work with Amsterdam UMC to develop AI, using data she collects from her other employer, Erasmus MC. 

She combines the best of both worlds, she says. ‘I see myself as a bridge builder between these two institutions. In Rotterdam, we conduct a lot of long-term population research. In Nijmegen, where I have been working since 2016, we are incredibly good at lab work and genetics. This way, we strengthen each other and develop the right care for the right patient.’ 

Let science work

Caroline Klaver says, ‘Scientific research is enormously important for academic centers. New discoveries have so much spin-off in patient care and education. Given the challenges we face in healthcare, we must cherish science in academia. It is not just a hobby, something fun to engage in. It gives us, as an academic hospital, our raison d'être. But not only that. American research showed that every dollar invested in innovation and research by former President Barack Obama yielded seven dollars for society. What I want to say is: the costs come before the benefits. If we don't want to invest, we will lose in the long run. Not just as scientists, but also as a government and society as a whole.’ 

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