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Kristen Totonelly, Laimeng Lee, Andy T. Cheng, Debora L. Nickla; Evidence that Dopamine Acts Upstream of Nitric Oxide in the Signal Cascade Mediating Ocular Growth Inhibition. Invest. Ophthalmol. Vis. Sci. 2012;53(14):4660.
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Evidence from animal models of myopia indicate that both dopamine and nitric oxide (NO) may play a role in ocular growth inhibition: quinpirole (D2 agonist) prevents the development of both form deprivation- and negative lens-induced myopia, and nitric oxide synthase (NOS) inhibitors prevent the growth inhibition that results from imposing myopic defocus using positive lenses (Nickla et al., 2009). We sought to determine if dopamine and NO act on the same pathway, and if so, which is upstream.
One eye of 12 d-old chicks wore either a -10 D lens, or a translucent diffuser (FD) for 5 days. Each paradigm was divided into four groups and experimental eyes were injected daily for 4 days: (1) Quinpirole: 20 µl injections (FD: n=21; Lens: n=13); (2) Both: 10 µl quinpirole + 10 µl n-omega-propyl-L-arginine (n-PLA; nNOS inhibitor) (n=17; n=23); (3) N-PLA: 20 µl (n=4; n=10); (4) Saline: 20 µl (n=20; n=35). Ocular dimensions were measured using high frequency A-scan ultrasonography before, and on the last day immediately prior to and 3 hours after injections. Refractions were measured on the last day. In one lens experiment, NO was measured in eyecups using the in-NO amperometric system after the final measures.
As expected, quinpirole alone largely prevented the development of myopia in both paradigms (exp vs saline: FD: -3.4 D vs -6.2 D; Lens: -0.4 D vs -4.7 D; p<0.01 for both) due to the inhibition of the growth of the vitreous chamber (FD: 290 vs 364 µm; p=0.08: Lens: 277 vs 353 µm; p<0.05). By contrast, co-injecting quinpirole with n-PLA inhibited the effect of quinpirole: eyes became more myopic than with quinpirole alone (FD: -5.9 D vs -3.4 D; Lens: -3.5 D vs -0.4 D; p<0.05 for both) as a result of faster growth (FD: 401 vs 290 µm; Lens: 407 vs 277 µm; p<0.05). In the lens group, co-injections also prevented the quinpirole-induced transient choroidal thickening (0 µm vs 31 µm/3 hrs; p<0.05). In vitro, eyecups from quinpirole-injected eyes produced more NO over 24 hrs than those of their fellow controls (paired t-test; p<0.005).
The finding that the nNOS inhibitor blocks the inhibitory action of quinpirole on eye growth suggests that dopamine acts upstream of NO in the same pathway of the signal cascade mediating ocular growth inhibition.
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