Elsevier

Brain Research Reviews

Volume 32, Issue 1, 24 March 2000, Pages 121-129
Brain Research Reviews

Short review
Modulation of coupling between retinal horizontal cells by retinoic acid and endogenous dopamine

https://doi.org/10.1016/S0165-0173(99)00071-5Get rights and content

Abstract

The regulation of electrical coupling between retinal neurons appears to be an important component of the neuronal mechanism of light adaptation, which enables the retina to operate efficiently over a broad range of light intensities. The information about the ambient light conditions has to be transmitted to the neuronal network of the retina and previous evidence has indicated that dopamine is an important neurochemical signal. In addition, recent studies suggest that another important chemical signal is retinoic acid, which is a light-correlated byproduct of the phototransduction cycle. This review summarizes the latest findings about the effects of dopamine and retinoic acid on gap junctional coupling in the retinas of mouse, rabbit and fish.

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)

  • V Bex et al.

    Retinoic acid enhances connexin43 expression at the post-transcriptional level in rat liver epithelial cells

    Cell Biochem. Funct.

    (1995)
  • C.M Chresta et al.

    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

    (1995)
  • D.F Condorelli et al.

    Cloning of a new gap junction gene (Cx36) highly expressed in mammalian brain neurons

    Eur. J. Neurosci.

    (1998)
  • S.H DeVries et al.

    Modulation of an electrical synapse between solitary pairs of catfish horizontal cells by dopamine and second messengers

    J. Physiol.

    (1989)
  • C.-J Dong et al.

    The relationship between light, dopamine release and horizontal cell coupling in the mudpuppy retina

    J. Physiol.

    (1991)
  • C.-J Dong et al.

    Comparison of the effects of flickering and steady light on dopamine release and horizontal cell coupling in the mudpuppy retina

    J. Neurophysiol.

    (1992)
  • E.C.G.M Hampson et al.

    Dopaminergic modulation of gap junction permeability between amacrine cells in mammalian retina

    J. Neurosci.

    (1992)
  • E.C.G.M Hampson et al.

    pH-Gated dopaminergic modulation of horizontal cell gap junctions in mammalian retina

    Proc. R. Soc. Lond. [Biol.]

    (1994)
  • S. He, R. Weiler, D.I. Vaney, Gap junctional coupling and its regulation in horizontal cells of the mouse retina, J....
  • T.D Lamb

    Spatial properties of horizontal cell responses in the turtle retina

    J. Physiol. (London)

    (1976)
  • E.M Lasater et al.

    Dopamine decreases conductance of the electrical junctions between cultured retinal horizontal cells

    Proc. Natl. Acad. Sci. U.S.A.

    (1985)
  • S.C Mangel et al.

    Responsiveness and receptive field size of carp horizontal cells are reduced by prolonged darkness and dopamine

    Science

    (1985)
  • P McCaffery et al.

    Light-mediated retinoic acid production

    Proc. Natl. Acad. Sci. U.S.A.

    (1996)
  • Cited by (79)

    • Candidate pathways for retina to scleral signaling in refractive eye growth

      2022, Experimental Eye Research
      Citation Excerpt :

      It is increased in response to both myopigenic cues (Mao et al., 2012; McFadden et al., 2004; Seko et al., 1998; Troilo et al., 2006) and greater luminance (McCaffery et al., 1996), although these increases may occur through different pathways. Together, this implies that the regulation of many retinal processes by light may occur at the transcriptional level via atRA, including light adaptation of horizontal cells (Pottek and Weiler, 2000; Weiler et al., 1998, 1999, 2000) and the transcription of arrestin, a critical phototransduction protein (Wagner et al., 1997). Retinal atRA has been demonstrated to be increased after FDM and LIM in the guinea pig (Huang et al., 2011; Mao et al., 2012; McFadden et al., 2004) and chicken (Bitzer et al., 2000; Seko et al., 1998).

    • Connexin43 in retinal injury and disease

      2016, Progress in Retinal and Eye Research
    • Retina: Information processing: Horizontal cells

      2016, The Curated Reference Collection in Neuroscience and Biobehavioral Psychology
    • Gap junctional coupling in the vertebrate retina: Variations on one theme?

      2013, Progress in Retinal and Eye Research
      Citation Excerpt :

      Retinal gap junctions are of a particular interest to neuroscientists, since there is no other area in the nervous system where gap junctions are found in such a great quantity and participate so extensively in signal processing. A number of recent reviews have surveyed the electrical and/or network properties, tracer coupling and cell-to-cell connections of retinal gap junctions (e.g. Bloomfield and Völgyi, 2009; Cook and Becker, 2009; Demb and Pugh, 2002; Roerig and Feller, 2000; Söhl et al., 2000; Vaney and Weiler, 2000; Weiler et al., 2000). However, the phylogenetic aspects and/or conservation of these properties have not been reviewed for over 15 years since the seminal work of Cook and Becker (1995).

    View all citing articles on Scopus
    View full text