Characterization of retinoic acid neuromodulation in the carp retina

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.