The group of Monte Westerfield and Jennifer Phillips (University of Oregon, USA) demonstrated in zebrafish models for Usher Syndrome that mutations in various Usher genes affect the health of cells. In the cell proteins are produced in the endoplasmic reticulum (ER) and then transported to the correct place in the cell. In the ER, Usher proteins forma complex of proteins, which is transported as a whole. It seems that different Usher mutations, each type in its own way, prevent the forming of the correct (Usher) protein complex in the endoplasmic reticulum. This incomplete or not functioning protein complex cannot be transported and accumulates in the ER. This is called ER stress, because this accumulation is a heavy burden on the cell. It is expected that prolonged ER stress leads to the rods and cones in the retina as well as the hair cells in the inner ear dying slowly. It was also demonstrated that intense or bright light can accelerate the dying of cells in the retina. Therefore Monte Westerfield advises to wear sunglasses when the light is intense in order to protect the cells of the retina.

    The research group of Monte Westerfield (University of Oregon, Eugene, USA) studies the effect of CDH23 (= USH1D), USH1C and MYO7A (= USH1B) in the zebra fish model. It seems that various mutations in these genes prevent the production and transport of the protein complex, consisting of the three proteins mentioned, into and out of the ER. As a result of this, this incomplete protein complex accumulates in the ER, which leads to ER stress.

    Westerfield and colleagues want to test various medicines against Parkinson’s disease and Alzheimer’s disease in their zebrafish models for Usher Syndrome in follow-up studies. This medication has demonstrated that it can reduce ER stress. Expectations are this this will slow down the deterioration of the hearing and eyesight of the zebrafish. The development of this possible form of therapy is still in an early phase. Possibly, the findings can also be applied to Usher types 2 and 3. If this therapy appears to work, application of this may be possible prior to or in support of gene therapy.