Retinoic acid has light-adaptive effects on horizontal cells in the retina

Abstract

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.

Direct gating by retinoic acid of retinal electrical synapses

“…Given that multiple retinal cell types are capable of RA production (6,33,38,39), RA could affect electrical synaptic transmission in other retinal networks as well as in horizontal cells in vivo. Synthesis of RA is activated by light adaptation (6), and modulation by RA of morphological and physiological changes in horizontal cells suggest that RA is involved in light adaptation processes (7,8,18), perhaps especially during steady light adaptation, which dopamine does not mediate (40)(41)(42). In contrast to two other retinal neuromodulators, dopamine and NO, which affect both electrical and glutamatergic synaptic transmission in horizontal cells (14-16, 27, 28, 43, 44), RA acts specifically on electrical synaptic channels.…”

“…In the vertebrate eye, the RA signaling pathway is involved in early eye and photoreceptor development, through the activation of gene transcription that is mediated by nuclear receptors (1)(2)(3)(4)(5). In the mature retina, however, RA biosynthesis has been shown to be regulated by light (6), and RA has also recently been reported to affect the structure and physiological function of retinal horizontal cells through a nontranscriptional mechanism (7,8).…”

Molecular Mechanisms, Biological Actions, and Neuropharmacology of the Growth-Associated Protein GAP-43

“…The levels of released dopamine increase in almost all retinae with light adaptation, and dopamine mimics the effects of light in many instances [98]. In additon, retinoic acid was found to have light-adaptive effects on horizontal cells in the retina [98]. GAP-43 is also present in the sensory neurons of the cornea and may contribute to their remodeling [59].…”

“…The release of dopamine in the retina has been implicated in light/dark adaptation [58]. The levels of released dopamine increase in almost all retinae with light adaptation, and dopamine mimics the effects of light in many instances [98]. In additon, retinoic acid was found to have light-adaptive effects on horizontal cells in the retina [98].…”

Targeted Disruption of Aldh1a1 (Raldh1) Provides Evidence for a Complex Mechanism of Retinoic Acid Synthesis in the Developing Retina

“…Labeled Examination of visual function by electroretinography. In the adult retina, RA has previously been proposed to have light-adaptive effects that may modulate synaptic transmission of visual information (50,53). As Raldh1 protein normally persists in the adult dorsal retina (27), ERG was employed to examine the effect of a loss of Raldh1 on adult visual function.…”