Retinitis pigmentosa is a progressive blindness that affects more than one million people worldwide. A subtype of this disease is caused by mutations in genes that produce proteins responsible for maturation of RNA known as "splicing."
Researchers of the group of human molecular genetics at the Bellvitge Biomedical Research Institute (IDIBELL), led by Julian Ceron, have created a model of C. elegans worm with homologous gene alterations to human disease. Thus, this model opens up a promising avenue to understand the pathology and investigating new efficient therapies.
Local mutations, overall pathology
Genes that produce "splicing" proteins are expressed in all body cells. However, mutations in these genes affect the retina where they produce cell death, but not in other tissues. It is a mystery that has not yet been resolved.
The study, conducted mainly by PhD student Karinna Rubio and researchers Laura Fontrodona and David Aristizabal, combines transcriptomics, genetics, and cell biology to create a unique model in which to study retinitis pigmentosa.
Researchers have found that inactivating the homologous genes that cause the disease in the worm C. elegans, the animal also has a cell death specifically in one cell type.
Furthermore, this study proposes a new hypothesis, based on genomic instability of the affected cells to explain the specificity of the disease in the retina.
The investigator Julián Cerón explained that “the group is currently working on playing in C. elegans of mutations that exist in patients. The great similarity presented by these genes between humans and worms allow using the technique of CRISPR, to create an animal "avatar" with the same mutation in the patient. This is promising because C. elegans could become a platform on which to test drugs in a personalized way.”
Illustration: Specific cell apoptosis in worms treated with PRP-8 (RNAi). The PRP-8 gene is homologous to the human gene PRPF8 which is frequently mutated in retinitis pigmentosa. –IDIBELL-Bellvitge Biomedical Research Institute.
IDIBELL-Bellvitge Biomedical Research Institute News Release (11/04/15)
Abstract (RNA; (10/21/15))