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 8h. 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 +6D or -6D 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.

Change in the synthesis rates of ocular retinoic acid and scleral glycosaminoglycan during experimentally altered eye growth in marmosets.

PURPOSE: The purpose of this study was to examine the possibility that all-trans-retinoic acid (RA) in the eye is a signal related to changes in scleral extracellular matrix in a primate model of postnatal eye growth. METHODS: Juvenile marmosets (Callithrix jacchus) were divided into two experimental groups based on their response to monocular deprivation with diffusers: group 1, treated eyes becoming longer than fellow control eyes (n = 8), and group 2, treated eyes becoming shorter than control eyes (n = 7). Eyes were enucleated, dissected, and assayed for changes in the rates of scleral glycosaminoglycan (GAG) synthesis and ocular RA synthesis. The rate of incorporation of (35)SO4 into CPC-precipitable GAG in scleras was taken as a measure of the rate of synthesis of proteoglycans. In the same eyes the rate of RA synthesis in vivo was measured separately in the retina and the choroid/RPE (choroid with RPE attached) by HPLC. The effect of RA on the rate of scleral GAG synthesis was also examined in tissue-cultured pieces of sclera from additional marmosets. RESULTS: Induced changes in vitreous chamber length in diffuser-treated eyes correlated inversely with the rate of scleral GAG synthesis (P < 0.05) and directly correlated with the rate of RA synthesis measured separately in the retina (P < 0.05) and the choroid/RPE (P < 0.05). In group 1, the rate of scleral GAG synthesis was significantly lower (P < 0.01) in the treated eyes relative to control eyes, and the rate of RA synthesis in both the retina and the choroid/RPE was significantly higher (P < 0.01). In group 2, the rates of scleral GAG synthesis and RA synthesis in either the retina or choroid/RPE were not found to change significantly in the treated eyes compared with the control eyes. RA partially reduces the rate of scleral GAG synthesis in tissue-cultured primate sclera in a dose-dependent manner after several days. CONCLUSIONS: RA may play a role in the visual control of postnatal eye growth in primates, possibly by inducing changes in scleral extracellular matrix associated with increasing eye size. Decreasing growth rate below control levels may involve other mechanisms.

Retinoic acid signals the direction of ocular elongation in the guinea pig eye.

A growing eye becomes myopic after form deprivation (FD) or compensates for the power and sign of imposed spectacle lenses. A possible mediator of the underlying growth changes is all-trans retinoic acid (RA). Eye elongation and refractive error (RE) was manipulated by raising guinea pigs with FD, or a spectacle lens worn on one eye. We found retinal-RA increased in myopic eyes with accelerated elongation and was lower in eyes with inhibited elongation. RA levels in the choroid/sclera combined mirrored these directional changes. Feeding RA (25 mg/kg) repeatedly to guinea pigs, also resulted in rapid eye elongation (up to 5 times normal), and yet the RE was not effected. In conclusion, RA may act as a signal for the direction of ocular growth.