Oculomotor Abnormalities in a Sheep (Ovis aries) Model of Huntington's Disease: Towards a Biomarker for Assessing Therapeutic Efficacy

Background
Huntington’s disease (HD) is characterised by a loss of control of motor function that causes the presence of abnormal eye movements at early stages.

Objective
Here we measured eye movements in a sheep (Ovis aries) model of HD using a purpose-built, head-mounted sheep oculometer. This device allows us to measure saccades in sheep without the need for either behavioural training or head fixation. At the age of testing (6 years old), the HD sheep were pre-manifest.

Results
We found small but significant differences in eye movements between normal (control) and HD sheep during vestibular ocular reflex (VOR)- and vestibular-based post-rotational nystagmus (PRN)-based tests.

Conclusions
Two measures were identified that could distinguish normal from HD sheep; these were the number of PRN oscillations when tested in the dark and the gain (eye movement to head movement ratio) during the VOR when tested in the light. This is the first study, to our knowledge, in which eye movements have been quantified in sheep. It demonstrates the feasibility of measuring and quantifying human-relevant eye movements in this species. The HD-relevant deficits show that even in 'premanifest' sheep there are measurable signs of neurological dysfunction that are characterised by loss of control of eye movements.