Short reviewModulation of coupling between retinal horizontal cells by retinoic acid and endogenous dopamine
Introduction
Electrical coupling through gap junctions is very widespread in the retina, and direct intercellular communication plays important functions in retinal information processing (for reviews see Refs. 2, 36, 39). The complexity of electrical coupling in the retina was highlighted by the seminal discovery that gap junctions between horizontal cells are not simply low-resistance connections but can be modulated by neurotransmitters. Horizontal cells are second-order neurons, forming a large coupled network that feeds back onto the photoreceptors. The elegant combination of electrical recording, dye coupling and pharmacological lesioning experiments performed by Teranishi et al. 31, 32in the fish retina demonstrated that dopamine narrows the receptive fields of horizontal cells, and that this shrinkage is paralleled by decreased dye transfer between neighboring horizontal cells, indicating a modulation of the gap junction conductance. This key finding was subsequently corroborated in the retinas of other vertebrates 11, 15, 25and confirmed by direct measurement of a change in the coupling resistance between isolated pairs of horizontal cells [18]. In the mammalian retina, however, it has not been clear whether the regulation of the gap junctional conductance between horizontal cells is under endogenous dopaminergic control. It has only recently been demonstrated, in the light-adapted mouse retina, that the coupling is modulated by a sustained dopaminergic activity [16].
The receptive-field size of horizontal cells is also affected by the ambient light conditions. Strong background light narrowed the receptive field and restricted dye transfer in the mudpuppy and turtle retinas 11, 12, 40and recently in the rabbit retina [44]. This latter study and others 19, 33, 45, 46revealed that the correlation between the ambient light conditions and the coupling resistance is more complex than anticipated, probably reflecting the interaction of several distinct mechanisms. It is an obvious question to ask whether ambient light and dopamine affect the gap junctional conductance in a correlated way. This question is particularly pertinent because dopamine release in the retina appears to be regulated by the ambient light conditions (for review, see Ref. [43]). Several studies have addressed the interdependence of the two stimuli, but the results are not conclusive. For example, the effect of flickering light on the gap junctional resistance was blocked by dopamine antagonists, whereas that of a steady background light was not 1, 34, demonstrating that not all light-induced effects are attributable to dopamine.
This has spurred the search for additional light-adaptive signals that may communicate the ambient light conditions to the horizontal cell network. Nitric oxide (NO) has been suggested as a possible candidate and indeed, NO affects the coupling of horizontal cells 10, 26, but a direct link between NO and ambient light has not been established to date.
It has been shown that retinoic acid (RA) is produced in pigment epithelium cells of the mouse retina and that its formation is increased during background illumination [20]. Furthermore, a recent study has shown that RA produces light-adaptive changes in the fish retina [42]: RA induced the formation of spinules on the terminal dendrites of horizontal cells and reduced the length constant of the horizontal cell network. These observations strongly suggested a light-signaling role for RA in the retina. Given its effects on cell-to-cell coupling in other tissues, it was subsequently demonstrated that RA indeed affects the gap junctional coupling between horizontal cells [41].
This review summarizes the recent findings concerning the regulation of gap junctional communication between horizontal cells by endogenous dopamine and retinoic acid. In addition, the possible involvement of connexin32 in these regulatory mechanisms has been addressed using knock-out mice.
Section snippets
Dopaminergic modulation in the mouse retina
Previous reports showed that exogenous dopamine and light adaptation uncouple A-type horizontal cells in the rabbit retina 15, 44. The dopaminergic uncoupling, which required relatively high doses of dopamine (∼250 μM), operated only around pH 7.2 and was ineffective at pH 7.4. The D1 receptor antagonist SCH23390 completely blocked the modulation by exogenous dopamine but did not reveal a sustained modulation by endogenous dopamine [15]. Application of the same D1 receptor antagonist in the
Mammalian retina
Retinoic acid (RA) is a well known morphogenic factor that is important for the formation of the anterior–posterior axis in vertebrate development. In the retina, RA is produced throughout life as a byproduct of the dark regeneration process (Fig. 4). Because the formation of RA by the enzyme retinaldehyde dehydrogenase is an irreversible process, the amount of RA correlates with the amount of the substrate retinaldehyde and therefore with light exposure. This correlation has been confirmed for
Conclusions
The visual system functions over a wide range of light intensity that greatly exceeds the operating range of individual neurons. The necessary adaptational processes take place both in the transduction process within the photoreceptors and also in the retinal neuronal network, where modulation of electrical coupling appears to play an important role [30]. The horizontal cells adjust the sensitivity of the photoreceptors through a negative-feedback pathway. Each horizontal cell receives input
Acknowledgements
The work presented in this review has been supported by grants from the Deutsche Forschungsgemeinschaft, the Volkswagen-Stiftung, the German-Israeli Foundation, the Australian Research Council and the National Health and Medical Research Council (Australia).
References (47)
- et al.
The modulation of intercellular coupling in the retina
Semin. Cell Dev. Biol.
(1998) - et al.
Retinoic acid modulates gap junctional permeability: a comparative study of dye spreading and ionic coupling in cultured cells
Exp. Cell Res.
(1991) - et al.
Evidence for a posttranscriptional effect of retinoic acid on connexin43 gene expression via the 3′-untranslated region
FEBS Lett.
(1997) - et al.
Regulation of connexin31 gene expression upon retinoic acid treatment in rat choriocarcinoma cells
Exp. Cell Res.
(1996) - et al.
Effects of nitric oxide on the horizontal cell network and dopamine release in the carp retina
Vision Res.
(1997) Many diverse types of retinal neurons show tracer coupling when injected with biocytin or neurobiotin
Neurosci. Lett.
(1991)- et al.
Effects of background illuminations on the receptive field size of horizontal cells in the turtle retina are mediated by dopamine
Neurosci. Lett.
(1992) - et al.
Background illumination reduces horizontal cell receptive-field size in both, normal and 6-hydroxydopamine-lesioned goldfish retinas
Vis. Neurosci.
(1991) - et al.
Reduction of connexin43 expression and dye-coupling during neuronal differentiation of human NTera2/clone D1 cells
J. Neurosci. Res.
(1997) - et al.
Differential expression of gap junctions in neurons and astrocytes derived from P19 embryonal carcinoma cells
Dev. Genet.
(1997)
Retinoic acid enhances connexin43 expression at the post-transcriptional level in rat liver epithelial cells
Cell Biochem. Funct.
Retinoic acid and phorbolesters induced hyperphosphorylation of topoisomerase II-alpha is an early event in HL-60 human leukaemia cell differentiation: effect on topoisomerase activity and etoposide sensitivity
Leukaemia
Cloning of a new gap junction gene (Cx36) highly expressed in mammalian brain neurons
Eur. J. Neurosci.
Modulation of an electrical synapse between solitary pairs of catfish horizontal cells by dopamine and second messengers
J. Physiol.
The relationship between light, dopamine release and horizontal cell coupling in the mudpuppy retina
J. Physiol.
Comparison of the effects of flickering and steady light on dopamine release and horizontal cell coupling in the mudpuppy retina
J. Neurophysiol.
Dopaminergic modulation of gap junction permeability between amacrine cells in mammalian retina
J. Neurosci.
pH-Gated dopaminergic modulation of horizontal cell gap junctions in mammalian retina
Proc. R. Soc. Lond. [Biol.]
Spatial properties of horizontal cell responses in the turtle retina
J. Physiol. (London)
Dopamine decreases conductance of the electrical junctions between cultured retinal horizontal cells
Proc. Natl. Acad. Sci. U.S.A.
Responsiveness and receptive field size of carp horizontal cells are reduced by prolonged darkness and dopamine
Science
Light-mediated retinoic acid production
Proc. Natl. Acad. Sci. U.S.A.
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