Funding outcome

It is through the sense of sight that we, as humans, interpret and interact with our world. Vision begins with the reception of incoming light by specialized cells in the eye called photoreceptors, which include two subtypes: rods for low light vision and cones for high-acuity color vision. Photoreceptors have very unique shapes and specific sizes, ideally adapted to catching light and converting it to a message sent to the brain. In many childhood blindness-causing diseases, photoreceptors do not develop or maintain their proper structure, and in many cases the cells subsequently die. In our study, we are looking at the disease CDSR (cone dystrophy with supernormal rod response), which arises from mutations in one gene, KCNV2. Children with CDSR have generally poor eyesight that slowly becomes worse over time. The KCNV2 gene codes for the protein Kv8.2, which forms part of a potassium channel, and loss of Kv8.2 interferes with the ability of the photoreceptors to turn light into a neural signal that can be sent to the brain. However, we hypothesize that loss of Kv8.2 also changes the size and shape of the photoreceptors, which further disrupts their light-sensing function. Here, we are using zebrafish to study the mechanisms underlying CDSR. Zebrafish are vision-dependent predators with large eyes structured very similarly to human eyes. We created zebrafish CDSR models by introducing mutations into the homologous genes, kcnv2a and kcnv2b, and we will be studying both functional and structural changes to photoreceptors in the mutants. Moreover, we think that CDSR is an excellent candidate for gene therapy given the accessibility of the eye and the persistence of the photoreceptors, and our research will set the groundwork for that goal.