Characterization of retinoic acid neuromodulation in the carp retina

Abstract

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.

New therapeutic target for CNS injury? The role of retinoic acid signaling after nerve lesions

“…Direct activation (Eom et al, 2005) and inhibition (Lee et al, 1998) of the c-Jun N-terminal kinase (JNK) pathway were also observed. The mechanisms of these and other nongenomic effects (e.g., Battle et al, 2001;Dirks et al, 2004;Li et al, 1996;Weiler et al, 1998;Zhang and McMahon, 2000) lie beyond the focus of this review.…”

“…Of course, retinaldehyde plays a central role in light perception by photoreceptors, and RA itself is involved in light adaptation (Dirks et al, 2004;Weiler et al, 1998;Zhang and McMahon, 2000). Recently, the RA signal transduction process has been implicated in learning and memory (see McCaffery in this issue) and in several neurological and psychiatric diseases, including Parkinson's disease (Fisher, 1998;McCaffery and Dräger, 1994a), Huntington's disease (Luthi-Carter et al, 2000), schizophrenia (Galter et al, 2003;Goodman, 1998), Alzheimer's disease (Corcoran et al, 2004;Goodman and Pardee, 2002), depression (Hull and D'Arcy, 2003), and motoneuron disease (Corcoran et al, 2002b).…”

Structure, Distribution, and Function of Neuronal/Synaptic Spinules and Related Invaginating Projections

“…A number of factors control spinule formation including dopamine and protein kinase C (reviewed in Wagner and Djamgoz 1993; Popova 2014), as well as nerve growth factor (Haamedi et al 2001) and retinoic acid (Dirks et al 2004). Spinules may mediate “…feedback activity essential for the coding of antagonistic color information” (Popova 2014).…”

Light and myopia: from epidemiological studies to neurobiological mechanisms

“…Similarly, the impact of 20 min of bright room light retina and RPE samples revealed a strong RA activity when compared with samples kept in darkness. 218 Dirks et al 218 also noted that RA synthesis is lightdependent and DA-independent in the carp eye indicating that these two modulatory systems are not inter-dependent but act in parallel. Apart from this, studies in various animal models like chickens, [219][220][221] guinea pigs 222,223 and marmosets 224 revealed that changes in RA synthesis are species-dependent, where myopia induction led to a decreased RA level in chickens, and increased RA levels in guinea pigs and marmosets.…”