Paradoxical induction of dopaminergic cells following intravitreal injection of high doses of 6-hydroxydopamine in juvenile carp retina.

Histofluorescence studies were conducted on two groups of juvenile carp (body length, 12.7 and 6.6 cm on the average, respectively) during certain periods (3-11 months) of retinal growth, to evaluate the destructive effect of 6-hydroxydopamine on dopaminergic and indoleamine-accumulating cells. Within a certain range of doses (0.1-5.0 micrograms/eye) of the neurotoxin injected intravitreally, it was found to destroy both classes of cells in a dose-dependent manner: more cells disappeared with higher doses. However, a high dose (5-25 micrograms/eye) of the neurotoxin caused paradoxical events in the retina, inducing an appearance of clustered dopaminergic cells with various soma sizes and abnormally high regional density, disturbed laminar organization, and a facilitated growth rate at the retinal margin. A preliminary examination with [3H]thymidine labelling suggests that the high dose of 6-hydroxydopamine may cause severe damage to certain classes of cells including dopaminergic and indoleamine-accumulating cells, and that a metamorphic change of precursor cells (neuroblasts) in the outer nuclear layer is responsible for the induction of such abnormal dopaminergic cells as clusters.