Analysis of vertebrate eye movements following intravitreal drug injections. I. Blockade of retinal ON-cells by 2-amino-4-phosphonobutyrate eliminates optokinetic nystagmus.

1. Horizontal optokinetic nystagmus (OKN) was examined in alert rabbits and cats following intravitreal injection of 2-amino-4-phosphonobutyrate (APB), an agent which selectively blocks the light-responsiveness of retinal ON-cells while having little effect on OFF-cells. The retinal actions of APB were assessed independently by electroretinography. 2. In five rabbits, doses of APB sufficient to eliminate the b-wave of the electroretinogram reduced drastically the ability of the injected eye to drive OKN at all stimulus speeds tested (1-96 degrees/s). Impairment of OKN was apparent within minutes of the injection, remained maximal for several hours, and recovered completely in 1-7 days. OKN in response to stimulation of the uninjected eye alone remained qualitatively and quantitatively normal. 3. Following administration of APB, OKN in response to binocular stimulation displayed a directional asymmetry. Stimuli moving in the preferred (temporal-to-nasal) direction for the uninjected eye became more effective than stimuli moving in the opposite direction, indicating that the injected eye could no longer contribute to binocular OKN. 4. When rabbits viewed stationary stimuli through the APB-treated eye alone, episodes of slow (less than 1 degrees/s) ocular drift were observed, similar to the positional instability seen when rabbits are placed in darkness or when the retinal image is stablized artifically (12). 5. APB had little effect on OKN in normal cats. In two cats that had previously received large lesions of the visual cortex, however, APB eliminated the ability of the injected eye to drive monocular OKN. The extent of the impairment was similar to that seen in rabbits. Because the cortex is thought to contribute more to OKN in cats than in rabbits, this result suggests that the optokinetic pathways disrupted by APB project subcortically. 6. This study demonstrates that the integrity of retinal ON-cells is required to sustain normal OKN. The results are consistent with additional anatomic and physiological evidence suggesting that a particular subclass of retinal ganglion cells, the ON-direction-selective cells, may provide a crucial source of visual input to central optokinetic pathways.