Ambient light conditions affect the morphology of synaptic elements within the cone pedicle and modulate the spatial properties of the horizontal cell receptive field. We describe here that the effects of retinoic acid on these properties are similar to those of light adaptation. Intraorbital injection of retinoic acid into eyes of dark-adapted carp that subsequently were kept in complete darkness results in the formation of numerous spinules at the terminal dendrites of horizontal cells, a typical feature of light-adapted retinae. The formation of these spinules during light adaptation is impaired in the presence of citral, a competitive inhibitor of the dehydrogenase responsible for the generation of retinoic acid in vivo. Intracellularly recorded responses of horizontal cells from dark-adapted eyecup preparations superfused with retinoic acid reveal typical light-adapted spatial properties. Retinoic acid thus appears to act as a lightsignaling modulator. Its activity appears not to be at the transcriptional level because its action was not blocked by actinomycin.

Visual sensation in vertebrates starts with the isomerization of 11-cis retinaldehyde into all-trans retinaldehyde. Aldehyde dehydrogenases, present in the pigment epithelium and some retinal cells, convert all-trans retinaldehyde into all-trans retinoic acid (at-RA). Evidence in the retina and the hippocampus has accumulated, showing that at-RA, besides being a morphogenetic factor, also acts as a neuromodulator. In mature retina, at-RA affects visual processing by acting on gap junctional conductances and the synaptic transfer between photoreceptors and horizontal cells. We present evidence supporting a neuromodulatory role of at-RA in the carp retina. High performance liquid chromatography (HPLC) measurements and an RA bioassay indicate a light dependency of at-RA formation, which can explain the observed effects of at-RA on spinule formation at horizontal cell dendrites in this retina. Furthermore, inhibiting endogenous metabolism and catabolism of at-RA affects formation and persistence of spinules in a way, supporting a direct involvement of at-RA in this light-dependent mechanism of synaptic plasticity. The action of at-RA, however, seems independent of the dopaminergic system, known for its light-signaling role in the retina, because at-RA effects on spinule formation persisted in retina depleted of dopaminergic neurons or in the presence of haloperidol. Together, these data indicate that at-RA acts effectively as a direct neuromodulator in carp retina, transmitting information about ambient light conditions to the neuronal retina.