Funding outcome

Vision is central to our interactions with the world around us and it all begins with photoreceptors, the light-detecting cells at the back of the eye. Photoreceptors have unique and complicated cellular architecture. Unfortunately, humans cannot regenerate photoreceptors and their death leads to irreversible vision loss. Integral to photoreceptor function and survival is maintenance of their large sensory ending. Here, I study finger-like cellular protrusions, microvilli, that surround this light-detecting compartment. We know surprisingly little about their function, yet recent research proposes that microvillar disruption underlies loss of sight in Usher Syndrome Type 1. Usher Syndrome is the most common of combined hearing and vision loss, with Type 1 being the most severe and earliest onset. To develop effective treatments for vision loss in Usher Syndrome, it is essential to understand functions of the Usher proteins and how their disruption results in photoreceptor death. I selected zebrafish as the model for this project, as their eyes are anatomically very similar to human eyes. To better understand photoreceptor microvilli and their association with the sensory ending, I am characterizing their features in developing and adult fish. I will study the Usher Type 1 gene Espin by changing its expression and analyzing the effect on photoreceptor microvilli, sensory endings, and survival. I will access visual capacity in these fish by performing electroretinography, a common diagnostic tool for patients with vision problems. In summary, the goal of my project is to learn more about photoreceptor biology and the mechanisms that lead to vision loss in Usher syndrome.