Light modulation, not choroidal vasomotor action, is a regulator of refractive compensation to signed optical blur.

<bold>Background and Purpose: </bold>The nitric oxide system has two proposed sites and mechanisms of action within the ocular growth/refractive compensation platform-neuromodulatory effects on retinal physiology, and vascular/smooth muscle effects in the choroid. The relative contribution of these mechanisms are tested here with drugs that perturb the nitric oxide system and with slow flicker modulation of the ON and OFF pathways of the retina.<bold>Experimental Approach: </bold>Intravitreal injection of saline or 900 nmol N(G) -nitro-L-arginine methyl ester or L-arginine in saline was followed by monocular defocus with ±10 D lens (or no lens), from days 5-9 under standard diurnal (SD) or daytime 1 Hz ramped flicker conditions. Biometric, electrophysiological and histological analyses were conducted.<bold>Key Results: </bold>After 4 days of SD conditions, both drugs enhanced electroretinogram (ERG) b-wave cf. d-wave amplitudes compared with saline and reduced refractive compensation to -10 D lenses. Under flicker conditions compensation to +10 D lenses was suppressed. Choroidal thinning was observed in the drug, no lens groups under SD conditions, whereas choroidal thickening was seen in most groups under flicker conditions, irrespective of refractive outcomes.<bold>Conclusions and Implications: </bold>As choroidal thickness was not predictive of final refractive compensation across any of the variables of drug, defocus sign or light condition, it is unlikely that choroidal thickness is a primary mechanism underlying refractive compensation across the range of parameters of this study. Rather, the changes in refractive compensation observed under these particular drug and light conditions are more likely due to a neuromodulatory action on retinal ON and OFF pathways. [ABSTRACT FROM AUTHOR]