Visually induced changes in components of the retinoic acid system in fundal layers of the chick

Eye growth is visually regulated via messengers that are released from the retina. The retina involves a yet unknown algorithm to analyse the projecte d image so that the appropriate growth rates for the back of the eye are en sured. One biochemical candidate that could act as a growth controller, is retinoic acid (RA). Previous work (Seko, Shimokawa and Tokoro, 1996; Mertz et al., 1999) has shown that retinal and choroidal RA levels are indeed pre dictably changed by visual conditions that cause myopia or hyperopia, respe ctively. We have studied in which fundal tissues aldehyde dehydrogenase-2 ( AHD2) and retinaldehyde dehydrogenase-2 (RALDH2), enzymes involved in RA sy nthesis, are expressed and at which levels the effects of vision on RA leve ls may be controlled. Using Northern blot analysis, we have found that the retinal mRNA level of the AHD2 is up-regulated after 3 days of treatment wi th negative lenses (negative lenses place the image behind the retina). The abundance of the retinal mRNA of a RA receptor, RAR-beta, was up-regulated already after 6 hr of treatment with positive lenses (positive lenses plac e the image in front of the retina). The up-regulation persisted for at lea st 1 week. Finally, we have studied the effects of an inhibitor of RA synth esis, disulfiram, on the visual control of eye growth. We found inhibition of myopia as induced by frosted goggles ('deprivation myopia') but no signi ficant inhibitory effects on refractive errors induced by +7D or -7D lenses . Our results are in line with the hypothesis that RA may play a role in th e visual control of eye growth. The RA system differs from a number of othe r candidates (dopamine, cholinergic agents, opiates) in that it distinguish es between positive and negative defocus, similar tea the immediate early g ene ZENK (Stell et al., 1999). The exact time kinetics of the changes have still to be worked out since it is possible that the changes in RA relate t o already occurring changes in growth rather than to initial steps of the s ignaling cascade. (C) 2000 Academic Press.