Funding outcome

KCNV2 retinopathy is characterized by early childhood onset of severe vision loss. In particular, patients suffer from color blindness, loss of central vision, and hypersensitivity to light. The disease is caused by mutations in a single gene, KCNV2, which encodes a potassium channel subunit. Without the gene, the light-detecting photoreceptor cells in the eye can no longer respond properly to light. However, the symptoms of the disease are unique and the underlying mechanisms are unclear. One of the key questions is why cones photoreceptors, which mediate high-acuity colour vision, are significantly more vulnerable than rod photoreceptors, which mediate low-light vision. An understanding of the difference could provide avenues for preserving cone function. To learn more about KCNV2 retinopathy, and in the process gain insight into the fundamental biology of photoreceptors, the Hocking lab has created zebrafish models of the disease. A zebrafish eye is very similar to a human eye, making it an excellent basis for research into ocular diseases. Zerbrafish have two versions of the KCNV2 gene, kcnv2a and kcnv2b, which may be advantageous because we have evidence to suggest that kcnv2a functions in rods, while kcnv2b functions in cones, allowing us to separate the roles for KCNV2 in each cell type. In this project, we will 1) confirm the rod and cone-specific expression of kcnv2a and kcnv2b using custom-made antibodies, 2) conduct electroretinography on kcnv2a and kcnv2b mutant zebrafish to examine photoreceptor function, and 3) use histology to look at changes to the rod and cone cells in the mutant zebrafish. The eye is an accessible organ for localized treatment (e.g. gene therapy or drug delivery), increasing the importance of understand the biology of ocular disease.