Age-related macular degeneration (AMD) is the leading cause of irreversible visual
impairment in older people. Susceptibility to AMD is dependent on a combination of genetic components
and environmental factors with role attributed to retinal pigmented epithelium (RPE), immune cells and
vasculature. Several genome-wide association studies (GWASs) have been applied to AMD, resulting in
the identification of ~50 loci, that are significantly associated with increased risk. For most of these loci,
the causal variants, their mode of action, and the affected target genes are unknown. This gap is partly
due to the lack of an appropriate model to mimic AMD pathology. We propose to establish an engineered
tissue model for the human RPE-vascular unit. This will allow us to substantially improve our
understanding of AMD pathology and genetic predisposition by identifying causal risk SNPs within
GWAS-determined AMD-risk loci, detect their target genes, and elucidate the biological processes that
are affected by them. Moreover, modeling complex human diseases in an engineered tissue model will
be an essential step toward developing and testing new therapies. The research strategy is based on the
combination of new technologies; 3D printing of tissues, stem-cell and genome editing technologies and
cutting-edge genomic techniques. This project holds great promise for AMD research: the identification
of causal variants, target genes, and molecular pathways will improve our understanding of the molecular
mechanisms involved in AMD; to significantly enhance our capability for early identification of
individuals at high risk, intervention and disease prevention, all key visionary goals for personalized
medicine.
Modeling complex blinding human disease AMD in an engineered tissue – to uncover disease mechanisms and develop personalized treatments.
Modeling complex blinding human disease AMD in an engineered tissue - to uncover disease mechanisms and develop personalized treatments.
Prof. Ruth Ashery-Padan and Prof. Tal Dvir
Department of Human Molecular Genetics and Biochemistry, Faculty of Medicine, Life Science Institute, Sagol School of Neuroscience
We study the gene networks that transform the embryonic cells into a complex, differentiated organ. We focus on exploring this question by studying the process of eye development as a model for organogenesis. We apply cutting-edge technologies including mouse genetic tools (Cre/loxP), molecular biology, and microarray analysis to identify and functionally characterize genes that regulate the development of the eye in mammals. Understanding the normal developmental regulation of the different eye structures is essential for understanding visual disorders and designing treatments for ocular phenotypes including retinal degeneration, glaucoma and cataracts, all of which are leading causes of blindness.