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Regan S. Ashby, Katrina L. Schmid, Ian G. Morgan; Drugs Known to Prevent Experimental Myopia also Prevent the Down-Regulation in Retinal ZENK mRNA Expression. Invest. Ophthalmol. Vis. Sci. 2012;53(14):3428.
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We have previously reported that the injection of muscarinic cholinergic antagonist atropine and the non-specific dopaminergic receptor agonist ADTN reverses the down-regulation in the retinal expression of the immediate-early gene ZENK that is normally observed during the development of form- deprivation myopia (FDM). We have now determined that both the muscarinic cholinergic antagonist pirenzepine and the GABAC receptor antagonist (S)-4-ACPBPA, which retard the development of experimental myopia, also prevent the down-regulation of retinal ZENK expression during the development of FDM.
Chickens were anaesthetised with isofluorane before 10µL of pirenzepine (165 mM), (S)-4-ACPBPA (35 nmol), or distilled water (vehicle) was injected into the vitreous chamber of the left eye, immediately prior to fitting translucent diffusers. After 1h, 5 individual retinal samples were collected from each group. ZENK mRNA levels in the retinal tissue were determined by real time RT-PCR. Results were normalised against β-actin and HPRT.
Following 1hr of FDM, ZENK mRNA levels in the chicken retina were reduced by ~45%. The injection of pirenzepine or (S)-4-ACPBPA, immediately prior to the attachment of the translucent diffusers, not only prevented the suppression of ZENK expression, but increased ZENK mRNA levels above control levels to ~120% and ~390% respectively. In control retinas, in which translucent diffusers were not fitted, injection of either compound had no effect on ZENK expression.
ZENK mRNA levels in the chicken retina were significantly down-regulated after 1hr of FDM. This rapid down-regulation in ZENK expression is reversed by the injection of the muscarinic cholinergic antagonists atropine and pirenzepine, the dopaminergic agonist ADTN and the GABA antagonist (S)-4-ACPBPA, all of which are known to retard the development of experimental myopia. These drugs increased ZENK expression above control levels, similar to that seen during periods of reduced rates of ocular growth. Because of the rapid responses, these results suggest that muscarinic and GABAergic antagonists and dopamine agonists act at retinal sites in preventing the development of myopia.
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