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P. Damyanova, G. E. Lytle, B. Dhillon, D. L. Nickla; The Effects of Various Inhibitors of the Nitric Oxide Synthase Isoforms on the Compensatory Choroidal Response and Scleral Proteoglycan Synthesis. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5928.
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© ARVO (1962-2015); The Authors (2016-present)
In chickens, the choroid plays a role in emmetropization, pushing the retina towards the image plane. There is evidence that nitric oxide plays a role in this process as the non-specific nitric oxide synthase (NOS) inhibitor L-NAME inhibits the response to positive lenses (Nickla & Wildsoet; 2004). Preliminary studies using more specific inhibitors showed that the nNOS inhibitor TRIM did not inhibit the choroidal response, and in fact, may have augmented it (Lytle & Nickla, ARVO 2005). The purpose of this study was to elucidate which of the NOS isoforms are involved in mediating the changes in choroidal thickness.
To clarify the effects of TRIM, we injected it (0.3 µmol) into untreated eyes for 3 days. Other inhibitors used were Nw-propyl-L-arginine (nNOS), L-NIO (eNOS) and L-NIL (iNOS) (0.6 µmol). These drugs were injected intravitreally into eyes wearing +10 D lenses on day 1; lenses were worn for 3 days. All injections were 30 µl; saline injections were used as controls. High frequency A-scan ultrasonography was done at 0, 7, 24 and 48 hrs. Scleras were dissected and 6 mm punches were cultured in S35-labeled medium for 2 hrs, and proteoglycan (PG) synthesis assayed as previously described.
TRIM had an anomalous effect on the choroid of normal eyes, causing an increase in thickness after 7 hrs (drug vs saline: 84 vs -14 µm; p<0.05). This was concomitant with an inhibition in scleral PG synthesis (drug vs saline: 7752 vs 11128 DPM; p<0.005). On the contrary, the other nNOS inhibitor, Nw-propyl-L-arginine, had a similar effect as that of L-NAME, inhibiting the choroidal expansion at 7 hrs (change in thickness, drug vs saline: 13 vs 135 µm; p<0.05); choroids began to respond by 24 hrs (drug vs fellow controls: 57 vs -20 µm; p<0.05). It also inhibited the refractive compensation (3.2 D vs 5.4 D; p=0.05). PG synthesis tended to be higher in these eyes (6943 vs 3828 DPM; one-tailed t-test p=0.07). Neither L-NIO nor L-NIL had a significant effect on the choroidal response, nor were there effects on axial length or scleral PG synthesis.
The effect of TRIM is not consistent with the action of a NOS inhibitor in this system, however the increase in choroidal thickness is consistent with the inhibition in scleral growth and strengthens the hypothesis that the two mechanisms are linked. The similar effect of Nw-propyl-L-arginine to L-NAME is consistent with nNOS mediating the compensatory choroidal response in emmetropization.
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