Discovery and implementation of liquid biomarkers for use in Fuchs endothelial corneal dystrophy

Fuchs endothelial corneal dystrophy (FECD) is a common degenerative eye disease and the only treatment for preventing blindness is corneal transplantation. In our project, we aim to discover a biomarker signature of FECD that can be detected in the patient’s aqueous humour and develop a disease model that can be used to better understand this complex disease. This collaborative project brings together MUMC+ and Emendo, an exciting biotechnology company, dedicated to developing gene editing therapies for diverse diseases.

FECD affects 5% of the Dutch population and its typical age of onset is in the fifth or sixth decades of life, with most patients in Europe undergoing corneal transplantation in their seventies. In fact, due to ageing of the population, repeated corneal transplantation for FECD has become the second leading indication for corneal transplantation in Europe, further aggravating donor shortage. Our approach has the potential to identify persons at risk of developing or progressing disease, who are expected to benefit from therapeutic intervention with novel drug compounds. Success with this approach will limit the need for corneal transplants and chronic immunosuppression.

Aqueous humour is an accessible eye fluid in close contact with the corneal endothelial cells with a composition reflecting pathological processes. We will explore human aqueous humour as a source of molecular biomarkers for FECD. We plan to use high resolution mass spectrometry techniques to identify proteins in the aqueous humour that are present differently in individuals with and without FECD. In parallel we will also develop an in vitro disease model will be based on induced pluripotent stem cells generated from patients with FECD that are subsequently differentiated into corneal endothelial cells. This models give the possibility to test the effect of the medication on disease pathology and biomarker candidates.

Biomarker candidates that meet predefined selection criteria can be further developed into biomarker assays fit for implementation as (secondary) outcome measures in clinical trials using both the CRISPR based editing of Emendo or other companies working on gene editing for FECD. A disease model for FECD can be used to test future therapeutics and better understand this complex disease. Our approach may help to identify new biomarkers relevant for degenerative changes on the cellular level and support development of new precision medicines.