Project: A01

Site- and stage- specific chronic inflammation and fibrosis in Fuchs endothelial corneal dystrophy

Fuchs endothelial corneal dystrophy (FECD) is a bilateral gene- and age-related disorder leading to corneal edema and vision loss and represents the most common indication for corneal transplant surgery worldwide. FECD is characterised by accelerated loss of corneal endothelial cells and altered extracellular matrix (ECM) deposition of the underlying basement membrane. Recent studies demonstrate infiltration of the central endothelial layer by cells derived from the monocyte/macrophage lineage leading to early corneal endothelial activation of profibrotic pathways. The chronic low-grade inflammatory processes result in fibrotic remodeling of the corneal endothelial centre. Although the pathophysiology occurs mainly  in the endothelial centre and spreads centrifugally towards the periphery, a shortcoming of most molecular studies investigating gene-expression in FECD is that one identical pathological state is presumed for all cells within the whole endothelial monolayer. Our hypothesis is that there are significant site-specific differences in gene expression and pathology  in FECD that require different medical and/ or surgical approaches. To  improve therapeutic strategies, the proposed project A01 therefore aims to decipher the site-specific chronic inflammatory and fibrotic processes in FECD.

Key methods: single nuclei RNA sequencing, intra- and intercellular pathway analysis, expression profiling (RT-PCR, bulk-RNA sequencing),  tissue/cell culture,  cellular growth characterization upon ECM remodelling, immunofluorescence,  spatial proteomics by imaging mass spectrometry