The role of alpha2-chimaerin in wiring the ocular motor system

Eye movement disorders affect 1% of the human population. In severe cases, such disorders can result in amblyopia and partial blindness, and there is currently no effective treatment. Duane Retraction Syndrome (DRS) is a congenital form of squint in which horizontal eye movements are defective. Patients with DRS have abnormal wiring of the ocular motor system - the nerves and muscles that control eye movements.

We have shown that DRS can result from mutations in the cytoplasmic signalling molecule alpha2-chimaerin. We have demonstrated that transient manipulations of alpha2-chimaerin signalling in the chick and zebrafish model systems leads to defects in ocular motor wiring, akin to DRS in humans.

We are currently developing permanent models of DRS using stable transgenic zebrafish lines with loss- or gain-of-function of alpha2-chimaerin. The aim of this work is to determine the effects of alpha2-chimaerin signalling on the aetiology of DRS. We will map the neuroanatomy of the ocular motor system in these lines, and functionally test eye movements using the optokinetic reflex to determine the impairment in alpha2-chimaerin mutant fish.