Ocular Reflexes and Associated Behaviors

Nathans, 2008). An OMR is also initiated when the visual field moves across the retina and consists of involuntary movements of the head and/or body to assist in image stabilization (Kretschmer et al., 2013) and encompasses head movements initiated via the vestibulo-ocular reflex (VOR). These head movements stimulate the vestibular organs, which then send signals to the brain stem to generate compensatory eye movements in the opposite direction of the image motion (Iwashita et al, 2001 Cahill and Nathans, 2008). Both OKR and VOR collectively function to stabilize images across the retina over a wide spectrum of head and body movements (Iwashita et al., 2001 Cahill and Nathans, 2008). In the following sections we describe how these responses can be used to detect ocular toxicity in zebrafish and rodents. 

Several papers have recently been published on the validation and use of zebrafish (Danio rerio) larvae as early safety pharmacology screens in visual safety assessment (Berghmans et al., 2008 Richards et al., 2008). Importantly, zebrafish larvae are amenable to medium-to-high-throughput in vivo screening (Redfem et al., 2011). The larvae are small enough ( 1 mm in diameter) to be easily distributed and maintained in 96-well plates, which 

FIGURE 14.1 Diagram of the OKR apparatus. A projector plays a movie of black and white grating on to the inside of the drum, which surrounds a dish containing the 8-dpf zebrafish larvae immobilized in methylcellulose (inset). A camera records movies of the 

Assessing Oculotoxicity in Zebrafish Using the VMR The VMR assesses the locomotor movements of zebrafish larvae in response to lights being turned on and off (Emran et al., 2008 Yin et al., 2012). In brief, individual larvae (5 dpf that have been previously treated for 48 h with either vehicle or selected compounds) are placed in embryo medium in a well of a 96-well clear microtiter plate (12 fish/treatment group). The plate is then placed inside a recording chamber 

FIGURE 14.2 Diagram of the OMR apparatus, viewed from above and in cross section. Richards et al. (2008). Reproduced with 

---