Changing patterns of the retinoic acid system in the developing retina.

In retinas of embryonic rat and chick, as in the mouse, synthesis of retinoic acid is mediated by different dehydrogenases in dorsal and ventral portions, with the ventral pathways generating higher retinoic acid levels. In the mouse, the dorsal enzyme was previously found to be the aldehyde dehydrogenase class-1 isoform AHD-2 and the ventral enzyme an unknown acidic dehydrogenase activity. This acidic dehydrogenase activity is now shown to consist of an early and a later expressed form, with the early form being indistinguishable from the activity in the early embryonic trunk and heart regions. Expression of the acidic dehydrogenase in the eye is first detected at the optic pit stage (E8.0), a day before the appearance of AHD-2 in the optic vesicle. The acidic dehydrogenase accounts for most of the retinoic acid synthesis in the retina during embryonic and early postnatal stages; during later postnatal stages it disappears and in the adult retina all retinoic acid synthesis is mediated by AHD-2. HPLC measurements in mice show high levels of all-trans- and 13-cis-retinoic acid: at E14 the retina contains a total of about 0.5 microM retinoic acid, and levels in the adult retina are about fourfold lower. The dorso-ventral asymmetry extends also to the cellular retinoic acid binding protein CRABP I, which first appears in the early differentiating ganglion cells in central retina and in the later embryo shows transiently a ventro-dorsally receding pattern of expression.