Traditionally, mice are used as an animal model when studying disease. However, due to structural differences, mice are not an ideal model for understanding Usher syndrome (USH) in the eye. Zebrafish have been employed by USH researchers due to structural similarities, although they are not the perfect replication. In humans, mutations in the PCDH15 gene cause Usher syndrome type 1F, but in zebrafish the effects of PCDH15 are split into two genes, of which one causes retinal effects. The researchers found that zebrafish with mutations in this gene displayed progressively worsening damage to the cells that detect light (photoreceptors) early in development. The photoreceptor outer structures, which contain important proteins, detached from photoreceptors and were loose in the retina, notably before any cell death occurred. The effects on the cell structure were worse in eyes exposed to bright light than in those exposed to darkness, particularly in cones.
What this means for Usher syndrome: Having an animal model is an important step in research, both showing that it is possible to replicate retinal effects in an animal and because it is difficult or impossible to conduct invasive experiments on humans. Additionally, this study shows a mechanism potentially related to cell death in the damage to the photoreceptor structure.
