Abstract
Abstract: :
Purpose: To examine the role of dopamine receptors in early ocular development in the zebrafish. Methods: Dopamine receptor agonists and antagonists were applied to zebrafish embryos in buffered embryo media and incubated for 24 or 48 hrs. at 28oC, and then visually examined. Control embryos were incubated in embryo media for the same period without drugs for purposes of comparison. Results: Incubation in the D1 group receptor antagonist SCH23390 (1-10µM) produced small effects on eye size and rotation during development. The larvae were motile and responded to touch. Eticlopride, a D2 group antagonist was tested on larvae at doses of 1-100µM. When larval fish were incubated in eticlopride (10µM), the eye was reduced in size and the choroid fissure was poorly closed. Responses to tactile stimulation were reduced. When both D1 and D2 group receptors were blocked (eticlopride 10µM + SCH23390 10µM) severe retardation of eye development was observed. The optic fissure was incompletely closed, the eyes were unusually small in size, and incompletely rotated. Unlike control fish, the embryo did not respond to tactile stimulation. In contrast, incubation of embryos in the dopamine agonist apomorphine (1-10µM) caused a severe flattening of the optic cup, reduced ocular pigmentation, and retarded eye rotation. Eye sizes were similar to controls. Larvae responded to touch but were immotile. Incubation of larvae in D1- and D2- selective agonists had smaller effects on ocular development. In addition, many dopamine receptor drugs impaired blood flow in larvae, however the circulation quality did not correlate with eye size, suggesting these effects were secondary to dopamine's action on eye development. Conclusions: Dopamine receptors play a critical but poorly understood role in ocular morphogenesis, and early neural development in the larval zebrafish . We are currently examining the physiological and genetic mechanisms by which dopamine exerts its action during this critical developmental period.
Keywords: retinal development • dopamine • neurotransmitters/neurotransmitter systems