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J.R. Mertz, L.K. Geiger; Inhibiting Retinal Retinoic Acid Synthesis Pharmacologically Reduces Experimentally- induced Myopia in Chicks . Invest. Ophthalmol. Vis. Sci. 2003;44(13):2810.
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Purpose: It has been shown that levels of all-trans-retinoic acid (at-RA) in the retina and choroid are altered by visual manipulations that alter ocular growth rate in chicks. These changes go in opposite directions in the retina and choroid of eyes responding to manipulations that change growth rate. In this study we first tested the efficacy of various inhibitors of the enzymes that synthesize at-RA on retina and choroid in vitro. Second, we used intravitreal injections of two of these inhibitors to specifically target the retinal (as opposed to choroidal) at-RA pathway and looked at their effect on the responses to either negative lens-induced or diffuser-induced myopia. Methods: In vitro: Two classes of inhibitors were used: 4-methylpyrazole and ranitidine, both inhibitors of alcohol dehydrogenases, and phenyl ethyl isothiocyanate (PEITC) and diethyldithiocarbamic acid (DTTC), both inhibitors of aldehyde dehydrogenases. Eight mm punches of retina or choroid were incubated with tritiated retinol in the presence of various concentrations of the inhibitors, and levels of newly synthesized at-RA were determined by HPLC. Results: All compounds tested inhibited retinal at-RA (ranging from 80-100% inhibition) however, only ranitidine and PEITC inhibited choroidal at-RA (ranging from 60-95% inhibition). Intravitreal injections of DTTC inhibited the diffuser-induced myopia (-0.4 D vs -3.5 D; p<0.002). Injections of PEITC into lens-wearing eyes inhibited the lens-induced myopia (-1.7 D and –2 D vs –4 D and -5.25 D). Conclusions: The inhibition of retinal at-RA synthesis produced a significant reduction in diffuser- induced myopia and reduced the lens-induced myopia in the two eyes tested. These data suggest that retinal at-RA may be a signal molecule used during emmetropization.
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