Scientists at the University of Twente and Radboudumc are working on a new model that mimics the human retina: a retina-on-a-chip. The model could help better understand eye diseases and test new treatments.
The retina-on-a-chip should bring together the three main layers of the retina in one chip: the choroid, the pigment epithelium and the nerve layer. The first two layers have now been successfully integrated, while researchers are currently working on integrating the third layer. This approach is unique; previous research was mostly limited to single cell types rather than a fully functioning model of the retina.
Highly complex
The retina is one of the most complex structures in the human eye. It consists of multiple layers with different cell types, which work closely together to process visual information. In various eye diseases, this cooperation can become disrupted.
Traditional research into these conditions uses animal experiments in many cases. However, animals differ from humans in important ways, so the results are not always reliable for the human situation.
The new model being developed within the collaboration between the University of Twente and Radboudumc offers an alternative. By using human cells in a controlled environment, researchers can more accurately study how the retina responds to different stimuli, such as light, pressure and drugs. Among other things, the environment can be used to test therapies that can slow or even repair damage to the retina.
Microfluidic system
By the way, the retina-on-a-chip is not a digital microchip, but a microfluidic system. This is a small fluid-filled channel in which human cells can grow. These cells are arranged to mimic the structure of the real retina.
The advantage of this approach is that researchers can adjust conditions very precisely. For example, they can vary the amount of light or pressure and then observe how the retina responds. This allows them to track changes step by step, similar to what would happen in a clinical setting.
One of the biggest challenges in developing this model is the controlled assembly of all three layers of the retina: the choroid, the pigment epithelium and the nerve layer.
While combining single cell types in laboratory conditions has been done more often, integrating both the choroid, pigment epithelium and nerve layer in a structured way is new. The researchers now have a working prototype with the first two layers. However, the nerve layer is more complex as it is directly involved in signal transmission to the brain. Developing a functional and stable version of this will require further research efforts, the researchers report.
No more animal testing
A key advantage of the retina-on-a-chip is that it enables research without animal testing. This is scientifically valuable, as human cells better match the real situation in patients.
"What we are developing in the lab has all the components of the human retina relevant to the function of the eye. We want to know how it responds to diseases of the eye that may arise due to age or a hereditary component. This approach eliminates the need for animal experiments," the researchers report.
Studying rare eye diseases better
The model can also help better study rare eye diseases. For many of these diseases, few or no effective treatments are available because they are too rare to be studied on a large scale. The chip model can change this by testing specific cell combinations relatively easily, without the need for large patient groups.
The researchers still have some challenges to overcome. For instance, variations can occur in the production of models. Although there is progress in standardising production, it is not yet possible to make completely identical chips. This is important because consistency is necessary to ensure reliable research results.
Challenges
Scaling up production also poses challenges. For instance, it takes about 250 days to grow the required retinal cells from stem cells. The researchers are working on ways to speed up this process. In addition, it is necessary to ensure the quality of the nerve layer before it can be integrated with the other layers. Only when all three layers function stably can the model be fully used for research into eye diseases and possible treatments.
Clinical applications of the model are therefore still a long way off. However, the retina-on-a-chip already offers new opportunities for fundamental research. Even now that the model includes only the choroid and pigment epithelium, it can provide researchers with valuable insights into the processes underlying eye diseases. For patients with rare genetic disorders, this technology could eventually accelerate the development of targeted therapies.
