Abstract
Abstract: :
Purpose: Evidence shows that choroidal all-trans-retinoic acid (at-RA) may be part of the signal cascade in the visual regulation of ocular growth in chicks (Mertz and Wallman, 2000). It has also been shown that the compensatory changes in choroidal thickness may involve nitric oxide (NO): the non-specific NOS inhibitor L-NAME rapidly and transiently inhibits the myopic defocus-induced increases in choroidal thickness (Nickla et al., ARVO, 1999). Because these changes in thickness are consistently associated with changes in ocular growth rate it is possible that NO may be part of the signal cascade in growth regulation. If both at-RA and NO are involved, we hypothesized that L-NAME would result in a decrease in choroidal at-RA synthesis in eyes responding to myopic defocus. Methods: Chicks were made myopic by 5 days of form deprivation using diffusers. On the following 4 days the diffusers were removed for 2 hrs/day allowing 2 daily hrs of exposure to myopic defocus. One group received an intravitreal injection of 30 µl L-NAME (16 µM) prior to the defocus each day (n=4), the other group received saline (n=4). Refractive errors were measured with a refractometer at the start and end of the experiment. Ocular dimensions were measured with A-scan ultrasonography at various intervals. Eyes were dissected and 6-mm punches of choroid and retina were incubated for 1.5 hrs with tritiated retinol. Newly synthesized at-RA was determined by HPLC. Results: Eyes injected with L-NAME showed a significantly reduced degree of recovery from myopia compared to saline controls (change in RE: -1D vs +4.5D; p<0.005), preventing the defocus-induced reduction in growth rate. L-NAME also prevented the transient defocus-induced increases in choroidal thickness (2 hours: 8 µm vs 91 µm; p<0.05) although there was a small amount of thickening over the entire period (23 µm vs 100 µm/4 days; p<0.05). Choroids of L-NAME-injected eyes showed a significant reduction in the synthesis of at-RA compared to saline control choroids (267 vs 949 cpm; p<0.005). There were no significant differences in at-RA synthesis in the retinas. Conclusions: The inhibition of recovery from deprivation myopia by L-NAME resulted in the predicted decrease in choroidal at-RA synthesis, further evidence that at-RA is involved in eye growth regulation. This result also supports the hypothesis that NO may play a role in ocular growth regulation and may influence both choroidal thickness and at-RA synthesis.
Keywords: choroid • retinoids/retinoid binding proteins • myopia