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I. G. Morgan, R. S. Ashby; Atropine and ADTN Up-Regulate Retinal Zenk mRNA Expression - but Only in Eyes Developing Myopia. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1730.
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We have previously reported that atropine and ADTN rapidly increase retinal expression of the immediate-early gene ZENK, in eyes where ZENK mRNA expression has been reduced during the early stages of form-deprivation myopia (FDM), but not in control eyes (Exp Eye Res 2007;85:15-22). We have now determined if similar changes are seen during lens-induced myopia (LIM).
Chickens were anaesthetised with isofluorane before 10µL of atropine (25mM in the needle), 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene hydrobromide (ADTN, 10mM in the needle) dissolved in 1% ascorbic acid, or distilled water or 1% ascorbic acid as vehicles was injected into the vitreous chamber of the left eye, immediately prior to fitting -10D lenses. After 1h, 5 samples were collected from each group, with each sample containing two retinas, one from each of two animals. ZENK mRNA levels were determined by real time RT-PCR. Results were normalised against β-actin.
Following 1hr of LIM, ZENK mRNA levels in the chicken retina were reduced by 37%. The injection of atropine or ADTN, immediately prior to the attachment of lenses, not only prevented the suppression of ZENK expression, but increased ZENK mRNA levels above control levels to 117% and 165% respectively. In control retinas, injection of atropine or ADTN had no effect on ZENK expression.
ZENK mRNA levels in the chicken retina were significantly down-regulated after 1hr of LIM, as was the case in FDM. Similarly, ZENK expression was elevated in the eyes of chickens treated with atropine or ADTN prior to lens attachment, as was also the case in FDM. Neither atropine nor ADTN had an effect on ZENK expression in control retinas. This suggests that retinal circuits change significantly during the early stages of development of both LIM and FDM, increasing their sensitivity to atropine and ADTN. Under these conditions, atropine and ADTN induce changes in ZENK mRNA expression similar to those seen when eye growth is slowed by myopic defocus. These results show that even the very early molecular changes occurring during the development of FDM and LIM are similar, and also suggest that muscarinic antagonists and dopamine agonists act at retinal sites in preventing the development of myopia.
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