Effects of selective neurotoxins on eye growth in the young chick

We have determined the extent of retinal cell damage and eye growth after treatment with different neurotoxins. Day-old chicks received an intraocular injection containing 2, 10, 50, 100 or 200 nmol of kainic acid (KA), an excitotoxic analogue of glutamate. After 21 days, with 2 nmol KA damage was confined to a small proportion of bipolar cells, whereas with 10-200 nmol KA there was dose-dependent damage to amacrine cells, ganglion cells and photoreceptors. There was an increase in eye weight and size of the vitreal chamber with 10 nmol KA or more. In a similar protocol using 5, 50 or 200 nmol quisqualic acid (QUIS), there was massive loss of amacrine cells and slight loss of horizontal cells, and a large increase in the anterior chamber depth. A single dose of 200 nmol N-methyl-D-aspartate lesioned amacrine cells, but did not alter eye size. Thus, excitotoxins which have different retinotoxic effects also have different effects on eye size. In another study, we examined the effects of KA and QUIS on occlusion-induced eye enlargement. Treatment with 200 nmol QUIS alone resulted in increased depth of the anterior chamber. QUIS combined with occlusion for 3 weeks did not interfere with occlusion-induced growth of the vitreal chamber. Therefore, the loss of a large proportion of amacrine cells did not interfere with occlusion-induced growth. KA results in eye growth in its own right, but restricts occlusion-induced growth. These effects are associated with damage to photoreceptors, amacrine and bipolar cells and a small proportion of ganglion cells. Finally, we examined the effects of an intraocular injection of tunicamycin, a purported photoreceptor-specific neurotoxin in amphibia. Tunicamycin (0.1 or 1 mumg/eye) resulted in a flattened anterior chamber but did not affect growth of the vitreal chamber. Tunicamycin inhibited occlusion-induced growth, and treated retinae displayed massive disruption and loss of all cell types apart from a single row of pigmented retinal epithelium. We conclude that (a) normal and occlusion-induced eye growth may have separate mechanisms of action, (b) the vitreous and anterior chambers have different growth mechanisms, and (c) photoreceptors may play a critical role in occlusion-induced growth of the eye.