Abstract
Purpose: :
Myopia (nearsightedness), in which images of distant objects cannot be focused without optical correction, is caused by excessive elongation of the growing eye. To understand it we induce form-deprivation myopia (FDM) in animal models, such as young chickens, with a translucent diffuser. Dopamine (DA) and nitric oxide (NO) prevent FDM, probably by acting in series, since antagonist to either one alone stops the prevention of FDM by brief goggle-removal. Here we tested the hypothesis that NO prevents FDM in chicks through a DA-D2-receptor relay.
Methods: :
One eye of chickens 1-10 day-old was goggled with a diffuser; every 2nd day (total 3 times) we injected drug into the vitreous of the goggled eye and 1x PBS vehicle into the open fellow eye under O2-N2O-Isoflurane anesthesia. First we determined the optimal doses of NO-donor (SNAP, to prevent FDM) and DA-D2R-antagonist (Spiperone, to prevent the effect of 2 hr goggle-removal). Next, we gave optimal doses of SNAP and Spiperone simultaneously, leaving the diffuser on permanently; control animals had the goggle permanently on or off and were given no drug. One day after the third treatment, we measured refractive error, eye size and weight. We also determined similarly the optimal doses of DA-agonist, ADTN, and NOS-inhibitor L-NIO, and are testing the alternate hypothesis that activation of DA-D2R prevents FDM via a NO-releasing relay.
Results: :
Under the conditions of our experiments, SNAP and ADTN prevented FDM, while Spiperone and L-NIO blocked myopia-prevention by diffuser-removal for 2 hr; the optimal doses were: Spiperone, 5nmol; SNAP, 500nmol; ADTN, 3mM; L-NIO, 20uM. At these doses, Spiperone did not block myopia-prevention by SNAP. The parallel experiment on ADTN and L-NIO is in progress.
Conclusions: :
Since Spiperone did not block myopia-prevention by SNAP, NO does not prevent FDM via a DA-D2R relay. We are now determining whether a blocker of NO synthesis will block myopia-prevention by DA agonist, to reinforce the alternative hypothesis. These findings will lead to better understanding of the mechanisms underlying emmetropia and myopia, and may lead to novel therapies to prevent myopia.
Keywords: myopia • dopamine • nitric oxide