Effects of quisqualic acid on retinal ZENK expression induced by imposed defocus in the chick eye

Expression of the transcription factor ZENK in glucagon amacrine cells of the chicken retina is enhanced after treatment with positive spectacle lenses and reduced after treatment with negative lenses. ZENK may, therefore, have an important role in emmetropization. To learn more about its regulation, we have studied its expression after retinal intoxication with quisqualic acid (QA, a glutamatergic excitotoxin).

Lenses of either +7 or -7 D power were placed in front of the eyes of young chickens 6 days after intravitreal QA injections. By this time, QA had caused severe damage to the retina. After 2 hours of lens wearing, changes in ZENK immunoreactivity were measured by means of double staining. In another experiment, lenses were worn for 4 days to study the residual function of emmetropization.

QA injections caused a massive loss of cells in the inner nuclear layer and the ganglion cell layer but left the numbers of glucagon cells unchanged. Four of six QA-injected eyes became more myopic in response to wearing positive lenses, and all eyes with negative lenses also became myopic. QA caused a general reduction in ZENK expression, and there was no clear evidence that ZENK expression was still controlled by the sign of imposed defocus.

After severe destruction of the inner retina by QA, retinal image processing appeared to be reduced to blur detection with no sign, causing myopia with both types of lenses. QA must remove synaptic input to the glucagon cells, which is necessary to transmit the information on the sign of imposed defocus.