Thesis defense Marie Bannier-Hélaouët: Modeling the ocular surface with organoid technology

The production of tears is essential for maintaining a healthy ocular surface. Tears prevent the eyes from dehydrating and also contain antimicrobial components that protect the eyes against infections. Two ocular surface tissues involved in tear production are the lacrimal gland and the conjunctiva. If these structures fail to produce enough tear fluid, this can result in dry eye disease. Apart from being painful, it can ultimately affect vision as well.

Organoids of the ocular surface

Studying the function of the lacrimal gland and conjunctiva in the lab was difficult with the existing in vitroLiterally: in glass. In vitro research means that a process of the body is studied outside of the body. For example, cells can be used for these studies. models, so Bannier-Hélaouët and her colleagues set out to develop a better model of these tissues. They were the first to successfully produce organoidsMiniature organs that can be cultured in the laboratory. Organoids mimic the shape and function of an actual organ. Researchers use the structures to, for example, study the effects of medication on diseased organs. of the human lacrimal gland and conjunctiva. These miniature organs strongly resemble the tissues in the human eye and can even cry in a dish. “The organoids allow us to better understand the function of these tissues. For example, we applied a technique called single-cell sequencingA technique that researchers use to determine the activity of genes in individual cells. For example, they can use this information to determine why diseased and healthy cells function differently. to determine what individual cells in the organoids were able to do. We discovered that certain cells of the conjunctiva can produce antimicrobial components of tears, something that was previously only attributed to the lacrimal gland. It was not possible to study this before,” Bannier-Hélaouët explains.

Clinical applications

In the future, the organoids could offer opportunities for patients with severe dry eye problems. “The organoids could be used for a clinical trial, to investigate transplantation of the tissues to patients. This would be a very welcome solution for them, as there are currently no effective drugs for dry eye disease. For this, we’re currently focusing on the conjunctiva organoids. The lacrimal gland organoids still need more optimization, since this is a more complex tissue with a larger variety of cell types,” Bannier-Hélaouët says. The organoids are also a valuable tool for researchers to model diseases and discover new drugs. “We can infect the organoids with viruses to model eye infections and introduce mutationsErrors in the DNA. Mutations can, among other things, arise if the DNA is copied incorrectly or through external influences. For example, tumor cells often contain mutations that are beneficial for their growth. to study cancers of the ocular surface. This gives us opportunities to test new drugs for these diseases as well,” she concludes.

Waiting for the stars to align

Looking back on her PhD, Bannier-Hélaouët remembers struggling initially before her projects started to take shape. “I started out studying something completely different than what I ended up doing. Those projects didn’t work out, but I still learned a lot in the process. Then at some point it was like the stars aligned and things started working. It’s the peaks of adrenaline from getting good results that kept me going.” Her advice to anyone considering to do a PhD? “If you like science: go for it. Dare to try.”