News and outreach
scientific advancesBack
New study delves into causes and treatment of the most widespread blindness in Europe
published on 24/06/2024
This European study, published in the journal 'Genome biology', reveals the three-dimensional differences in the genome of the retinal components necessary for vision.
Two CABD teams participate in this work in which the three-dimensional structure of the genomes of the neural retina and the pigmented epithelium have been compared, identifying differences associated with the specific activation of genes involved in hereditary retinal disorders.
Authors from the CABD, from left to right, Ana Neto, Juan Ramón MArtínez-Morales, Pedro Martínez, Juan Tena and Silvia Naranjo
Hereditary retinal diseases are the major cause of blindness in Europe, a problem that affects 350,000 people. These diseases have long been considered incurable as vision loss due to these conditions was thought to be irreversible. However, recently there has been a great deal of interest in advancing novel treatments in this area, so much so that several research groups interested in these diseases have come together in a European network to learn more about these types of diseases. This list of experts includes researchers from the groups of Dr. Juan J. Tena and Dr. Juan Ramón Martínez-Morales, both from the Andalusian Center for Developmental Biology (CABD), a joint center of the Spanish National Research Council (CSIC), the Pablo de Olavide University (UPO) and the Andalusian Regional Government.
Correct vision depends on the interaction between the two components that form the retina: the neural retina and the pigmented epithelium. Although progressive blindnesses eventually converge in photoreceptor degeneration, they are frequently associated with gene activation in only one of the two components. In the last decade, it has become evident that gene activity is regulated by the three-dimensional structure of the genome. The genome, by dynamically folding in on itself, brings the regulatory elements (genetic switches that turn genes on and off) into contact with the right genes at the right time in the right cells. In this work, now published in Genome Biology, the three-dimensional structure of the genomes of the neural retina and the pigmented epithelium has been compared, allowing the identification of differences associated with the specific activation of genes involved in inherited retinal disorders.
“It has been observed that about 60% of the genes involved in hereditary retinal disorders present differences in the genomic structure of the neural retina and the pigmented epithelium. In fact, it is known that one of these genes is ABCA4, which causes a blindness called Stargardt's disease, for which there is currently no treatment”, indicates Dr. Martínez-Morales. Dr. Tena adds: “Until recently, the genetic study of this type of disease focused on alterations in the coding regions, i.e., the areas of the genome that house the genes that give rise to proteins. The problem is that many of the patients do not present variations in these regions, suggesting structural faults in the genome as a potential cause of these pathologies”. With this knowledge, the team has focused on looking for these structural variations that alter the way in which regulatory elements, which are non-coding regions, turn these genes off and on.
“The data analyzed in this project help to define the regulatory landscapes of genes expressed in the neural retinal compartments and pigmented epithelium in humans. These findings provide a very important reference to predict possible heritable structural variants that, in patients affected by retinal dystrophy, help to understand the molecular basis of their blindness and improve genetic counseling in relatives who have not yet developed the pathology”, concludes Dr. Pedro Martinez, one of the co-authors of the work.
Article
https://doi.org/10.1186/s13059-024-03250-6
D’haene, E., López-Soriano, V., Martínez-García, P.M. et al. Comparative 3D genome analysis between neural retina and retinal pigment epithelium reveals differential cis-regulatory interactions at retinal disease loci. Genome Biol 25, 123 (2024).
This press release was made in collaboration with CSIC Comunicación Andalucía y Extremadura
