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G.E. Lytle, D.L. Nickla; The Effect of the Neuronal Nitric Oxide Synthase Inhibitor TRIM on Chick Eyes Responding to Myopic Defocus . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3339.
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Purpose:In chicks, part of the compensatory response to defocus involves changes in the thickness of the choroid, which moves the retina closer to the image plane. Choroidal thickening in response to myopic defocus can be transiently inhibited by an intravitreal injection of the non–specific nitric oxide synthase (NOS) inhibitor L–NAME (Nickla & Wildsoet, 2004), supporting a role for the gaseous neurotransmitter nitric oxide (NO) in the response. The source of the NO could be either neuronal or endothelial. To address this question, we used TRIM (1–(2–trifluoromethylphenyl) imidazole), a relatively specific inhibitor of nNOS. Methods: TRIM (30 µl) was injected into one eye of 1–week old chicks (dose: 0.3 µmoles (n=7), 0.03 µmoles (n=8) and 0.003 µmoles (n=8); saline was used as a control (n=12)). +10D lenses were immediately fitted to the injected eyes. Ocular dimensions were measured using A–scan ultrasonography at time 0 (prior to lens–wear), 7 hrs, 24 hrs and 48 hrs post–injection. In a second experiment, eyes were deprived of form vision for 7 days. The diffusers were then removed and eyes injected with TRIM (0.3 µmoles) and measured as above. In a pilot experiment using the same experimental design as the lens experiment, N–methyl–L–arginine (L–NMMA, inhibitor of eNOS) was used (dose: 0.1 µmoles). Results: Unlike L–NAME, TRIM did not inhibit the choroidal response to myopic defocus induced by either positive lenses or prior form deprivation (lens exp., 7 hrs, 0.3 µmole drug vs saline: 114 µm vs 95 µm). Nor did it dis–inhibit the axial elongation (lens exp., 48 hrs: 84 µm vs 53 µm). However, similar to L–NAME, TRIM resulted in a significant transient inhibition of the growth of the anterior chamber over 24 hrs (0–24 hrs: –3 µm vs 66 µm) that was reversed by 48 hrs (0–48 hrs: 66 µm vs 83 µm). This effect was dose–dependent, with an ED50 of 10 µmoles. At the dose used, L–NMMA tended to inhibit the choroidal response over 24 hours. Conclusions:The compensatory choroidal and axial responses to myopic defocus do not appear to involve nNOS. Nitric oxide appears to have independent effects on the growth of the back of the eye and anterior chamber depth that involve different NOS systems and different mechanisms. We speculate that the choroidal response is mediated by eNOS and hence involves changes in fluid dynamics via the vasculature.
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