Modeling the ocular surface with organoid technology

Abstract

The eye surface consists of 4 distinct tissues: the cornea, the conjunctiva, the lacrimal gland and the meibomian gland. The role of the three latter is to produce tears in order to protect the transparent cornea. Tears harbor antimicrobial and lubricative properties that are essential to keep the eye surface healthy. When not enough tears are produced, this results in dry eye - which is a disease 1 in 3 adults experiences.

To understand how the lacrimal gland and the conjunctiva produce tears, we obtained biopsies from these organs and identified conditions under which the cells were able to expand in a dish. This process gave rise to so-called lacrimal gland and conjunctiva organoids, respectively. We found that these organoids produced both the aqueous and the mucous layers of the tear film, including a large and diverse repertoire of anti-microbial peptides. We could study genetic and infectious diseases in these, as well as transplant them in order to rescue either lacrimal gland or conjunctiva deficiencies. These newly-developed technologies help to understand the underlying principles of (the lack of) tear production, which could be tackled in a drug discovery approach. Organoids can also be used as a cell therapy product, in order to replace lost or damaged ocular surface tissue. We are taking this aspect to the next level and are working towards initiating a phase I clinical trial, using conjunctival organoids as a cell therapy product.

On a different note, we sequenced patient ocular surface tumors in order to identify the mutations that caused these. This information can now be used to offer patients with better-suited targeted therapies.