Vertebrate Visual System Function

Our laboratory is interested in the genetic analysis of vertebrate visual system development and function. We are using the zebrafish, a tropical freshwater teleost, as our model organism. The zebrafish is a getting increasingly popular among geneticists and embryologist for its easy maintenance, high fecundity, transparent embryos, and rapid embryological development. Since we are interested in visual system performance, we are using a behavioral assay to test for vision in zebrafish larvae. We mainly use the optokinetic response (OKR) stereotyped eye movements triggered by large field motion in the visual field common to all vertebrates.

 
Fig. 1. Adult zebrafish

We trigger such eye movements either by placing the larvae inside a drum fitted with a moving grating or by projecting computer generated motion stimuli onto a screen viewed by the larva. With our fish “movietheater” we can perform psychophysical experiments to determine various properties of the visual system, such as acuity, contrast sensitivity, and adaptation.

Using this assay we have tested a number of chemically mutagenized strains for their visual capabilities resulting in the identification of a number of heritable visually impaired mutant strains. Subsequent histological and electrophysiological analysis (by recording electroretinograms - sum field potentials of the retina) revealed that the majority of mutants display apoptotic cell death of photoreceptors. These blind mutants share a number of characteristics with human outer retina dystrophies. Other mutants show defects in signal propagation or in the connection of the retina to the brain proper (retino-tectal projection).

For instance one mutant strain with reversed eye movements was found to form no optic chiasm, since the wrong brain hemisphere is innervated by retinal ganglion cell axons. Another mutant was found be blind since no retinal ganglion cells can not generate action potential due to a defect of sodium conductance.

 
Fig. 2. Zebrafish movietheater to measure the optokinetic response under various visual stimuli

A number of mutant strains have visual defects as part of a syndrome, similar to human diseases; e.g. some strains are hypopigmented and have blood clotting defects in addition to deficits in vision.

We are currently genetically mapping these and other mutations to chromosomes with the aim to identify the disrupted genes that are causing the observed visual defects.

We hope to gain a deeper insight into the genetic control of visual system development and function. This information will hopefully also benefit our understanding of similar human eye diseases.

Fig. 4. The projection areas of retinal ganglion cell axons in the brain are labeled. In wild-type fish axons cross at the midline, while they fail to cross in the mutant (belladonna).
 
Fig. 3. Section through the visual system of a 5 day old zebrafish larvae