FRO 2014: The pathophysiologic role of SNORD115 and SNORD116 in late‐onset Fuchs' endothelial corneal dystrophy

This project aims to investigate the pathophysiologic role of SNORD115 and SNORD116 in late-onset Fuchs' endothelial corneal dystrophy (FECD). Whole-genome microarray expression analyses showed downregulation of several small nucleolar RNAs in CEn of FECD patients. Two of these, SNORD115 and SNORD116, regulate pre-mRNA editing and alternative splicing of serotonin receptor 2C (HTR2C), and play a role in Prader-Willi syndrome (PWS). Since the serotonin receptor 2C may regulate transport of fluids across the CEn, we will investigate whether the downregulation of these snoRNAs plays a similar role in FECD as it does in PWS. To this end, we will determine the expression of different splice variants of HTR2C in FECD versus normal controls. Furthermore, we will study the effect of SNORD115 and SNORD116 knockdown and 5-HT-2C receptor blockage in immortalised human corneal endothelial cells.