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DL Nickla, JR Mertz; All-trans-retinoic Acid in Chick Suprachoroidal Fluid Shows a Diurnal Rhythm . Invest. Ophthalmol. Vis. Sci. 2002;43(13):208.
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Purpose: In chicks, all-trans-retinoic acid has been implicated as a possible signal molecule in the visual regulation of eye growth: it is significantly higher in choroids of eyes slowing their growth, and lower in choroids of eyes increasing their growth (Mertz and Wallman, 2000). It is also a potent inhibitor of scleral proteoglycan synthesis in vitro. Because both scleral proteoglycan synthesis and axial elongation exhibit circadian rhythms (Nickla et al., 1998; 1999), and because changes in proteoglycan synthesis presumably underlie changes in ocular elongation (Rada et al., 1991; 1992), if choroidal retinoic acid is part of the signal cascade, then it may also show a diurnal rhythm in synthesis or secretion. We tested this hypothesis. Methods: Eyes were dissected at 6 am, noon, 6 pm and midnight (n=8 birds each; 2 eyes per bird were combined for one data point). 10-15 µl of suprachoroidal fluid was extracted from the eyes by placing a 36G needle into the choroid through the central posterior sclera, taking care not to penetrate the retinal pigment epithelium (Pendrak et al., 2000). For each time point, 2 animals were kept in darkness for 36 hrs prior to the dissection. Fluid was extracted with 2 volumes of chloroform-methanol 2:1 (v/v), and retinoic acid levels determined by normal phase HPLC analysis. Results: All-trans-retinoic acid levels in the suprachoroidal fluid were high at midnight and 6 am and low at noon and 6 pm (ANOVA, p<0.0001). Thus, the phase of the rhythm is approximately opposite that of the rhythm in axial length, which shows a peak at about noon and a trough at midnight (Nickla et al., 1998). This finding is consistent with choroidal retinoic acid mediating (at least partly) the diurnal changes in axial length, with a small time lag. The same pattern was seen in animals kept in darkness, indicating that the rhythm is circadian. Conclusion: These results further support a role for all-trans-retinoic acid in the regulation of ocular growth. Ascertaining the precise phase relationship between the rhythms in choroidal retinoic acid and scleral proteoglycan synthesis would increase our understanding of the molecular mechanisms underlying changes in ocular growth.
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