PgmNr Z6147: Zebrafish as a model for eye disease: congenital cataracts.

Authors:
Lindy K. Brastrom; C. Anthony Scott; Diane C. Slusarski


Institutes
Department of Biology, University of Iowa, Iowa City, IA.


Abstract:

Eye disease and visual impairment coupled with age-related vision loss are a significant public health concern. Modern genomics has enabled the identification of an unprecedented number of genetic variants, many of which are extremely rare, associated with blinding disorders. Zebrafish pose many advantages as a human eye disease model. Key among these are their rapid generation time, small size, eye structure similar to humans, and ability to screen many at a time. By 5 days-post-fertilization (dpf) zebrafish have quantifiable behavioral responses to visual stimuli. Our lab has adapted vision testing in zebrafish to facilitate high-throughput in vivo screens: Visual Interrogation of Zebrafish maNipulations (VIZN) and OptoMotor Response (OMR). VIZN uses interruptions in constant light to garner a startle response. This vision startle assay looks at the ability of the fish to see in a general capacity. Fish that are visually compromised will not respond to the interruption of light. Automated data collection and software to handle the large spreadsheets have been developed to provide optimization in the number of screens we can accomplish. While the VIZN assay works for blinding disorders, there is a need to test for partial vision loss such as those exhibited in cataracts. We are currently adapting OMR to assay partial vision loss. This is done by stripes of white and black passing under a plate of fish. Fish that can see will respond by orienting their body perpendicular to the lines. Vision impaired fish will be unable to respond and thus not orient themselves to the lines. The goal is to combine both assays to evaluate the spectrum of visual impairments. We are currently assessing conditions to test for partial vision impairment. These tests will allow us to screen many genes related to loss of vision quickly and efficiently using zebrafish.         .