B: Molecular Pathogenesis

Component B: Molecular pathogenesis

For USH, insight in the pathogenesis is limited for the associated retinitis pigmentosa. We aim to improve the knowledge on the disease mechanisms on different molecular levels. The identification of novel members of the USH interactome may unravel common cellular pathways in which USH protein are involved and provide candidates or modifier genes for USH and related retinal degeneration disorders as they are “guilty by association” (B1). We aim to identify the physiological function of USH proteins (B2) to provide handles for future therapy (component C) which may be important for USH since the size of several of the involved genes hampers classical gene augmentation therapy. We will analyze the subcellular localization of USH proteins and novel identified USH interaction partners (identified by P6) in retinas of non-human primates and human donors (B3). The combination of data obtained in component B will provide novel insights into the role of USH proteins in photoreceptor cells and may be helpful for the genotype-phenotype correlation.

Expected results: understanding the pathomechanism of USH, obtaining novel insights into the role of USH proteins in photoreceptor cells and valuable tools for the evaluation of the therapeutic strategies.