Acute effects of dietary retinoic acid on ocular components in the growing chick

When the eyes of chicks are induced to grow toward myopia or hyperopia by having them wear spectacle lenses or diffusers, opposite changes take place in the retina and choroid in the synthesis and levels of all-trans Retinoic Acid (RA). To explore whether RA plays a causal role in the regulation of eye growth, we fed young chicks RA (doses 0.5 to 24 mg/kg) either twice a day or on alternate days or only once. Refractive error was measured with a Hartinger refractometer; ocular length, lens-thickness and choroidal thickness were measured by A-scan ultrasound. The amount of RA present in ocular tissues was determined using HPLC. Oral delivery of RA effectively increased RA in ocular tissues within 8 h. During the first day after feeding RA at levels above 8 mg/kg, the rate of ocular elongation tripled, the choroid thickened and lens thickening was inhibited. The day following a dose of RA, the rate of ocular elongation was inhibited and the lens thickened more than normal. Nonetheless, the cumulative effect of repeated doses was that the eye became longer and the lens became thinner than normal, with no net change in refractive error. The rate of elongation was also increased by feeding 13-cis RA, and was reduced by citral, an inhibitor of RA synthesis. Surprisingly, birds fed RA while being kept in darkness also had normal refractive errors despite increased ocular elongation, and birds wearing either +6 D or −6 D spectacle lenses compensated normally for the lenses despite the enhanced ocular elongation caused by the RA. These results suggest that RA may act at the level of a coordinated non-visual regulatory system which controls the growth of the various ocular components, arguing that emmetropization does not depend entirely on vision.