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Report

Teaser, summary, work performed and final results

Periodic Reporting for period 2 - MYOP-PATH (Towards solving myopia: from genes to pathways using an integrated approach)

Teaser

Summary

Myopia (near-sightedness) is a growing public health issue due to its rapidly rising prevalence. In particular high myopia carries a significant risk of blindness for which there are no treatment options. The disease etiology of this trait is complex and largely unknown. We have identified a large number of disease loci and genes, which provide significant clues for pathogenic pathways. However, the direct functional effects of risk variants, their interaction with environmental factors, and their potential for intervention are unknown. In MYOP-PATH we aim to identify disease mechanisms that underlie myopia and create starting points for therapy. The research is subdivided into 3 sub-projects: (1) genetics; (2) genes and environment; and (3) functional studies in animals.

Work performed

The project is now running for 2 years and all three projects progressed significantly. The research team has a multidisciplinary background and has sufficient expertise to perform the proposed work as planned. We performed the largest GWAS meta-analysis on refractive error (RE) in an international consortium (N=160,420). The analysis yielded a total of 167 loci associated by single variant analysis and additional conditional analysis (GCTA-COJO), of which 86% replicated significantly in the large UK Biobank Study (N= 95,505). The loci provided evidence for light processing in the retina as the most significant pathway. This research resulted in a publication in the high impact journal Nature Genetics; the major author positions were covered by my research group. For project 2 we are currently analyzing data of our epidemiologic studies, and we are finding that genetic risk score shows significant interaction with lifestyle, indicating that genetic effects may be expressed more easily after an environmental trigger. For project 3 we are using both zebrafish and mouse models to study myopia. Both models with various genes knocked out have been acquired and first experiments are taking place. An important step was to acquire all equipment needed for intervention and functional assessment of myopization. The interdisciplinary character of the research group has facilitated cross talk and creativity and prompted integration of knowledge from human genetic studies to animal studies.

Final results

Integrating the results obtained from these genetic, epidemiologic, functional and molecular animal studies will advance our understanding of the underlying biology of myopia and by studying the key players for myopia will identify novel therapeutic targets to reduce the burden of high myopia.