pigmentosa (RP) is a major cause of blindness which effects one
in 3000 individuals worldwide. Mutations in RP-associated genes lead
to the premature death of photoreceptor cells, which starts in the
retinal periphery and progresses towards the center. This
progression often results in complete blindness.
The functions of RP-associated genes fall into five categories. One of them is splicing, but the relevance of this process for the pathogenesis of RP is still poorly understood. We aim to complement this understanding by analysis of the role of novel splice isoforms of RP-associated genes. Bioinformatics approaches, tissue-specific expression analysis, and characterization of mutations affecting novel exons of RP-associated genes are part of these studies. Furthermore, we developed a gene therapeutic approach to rescue splice defects.
Mutations in splice factors are known to exclusively cause RP, although their transcripts and proteins are ubiquitously expressed. This indicates specialized requirements of photoreceptor cells for accurate splicing. The functional relevance of splice factor mutations for the disease of RP is studied in cell and retinal explant cultures and will help to understand the role of splicing in the complex disease of RP.
Romain Da Costa (PhD student)
John Neidhardt (PhD)