Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Retinal network adaptation to bright light requires tyrosinase

Abstract

The visual system adjusts its sensitivity to a wide range of light intensities. We report here that mutation of the zebrafish sdy gene, which encodes tyrosinase, slows down the onset of adaptation to bright light. When fish larvae were challenged with periods of darkness during the day, the sdy mutants required nearly an hour to recover optokinetic behavior after return to bright light, whereas wild types recovered within minutes. This behavioral deficit was phenocopied in fully pigmented fish by inhibiting tyrosinase and thus does not depend on the absence of melanin pigment in sdy. Electroretinograms showed that the dark-adapted retinal network recovers sensitivity to a pulse of light more slowly in sdy mutants than in wild types. This failure is localized in the retinal neural network, postsynaptic to photoreceptors. We propose that retinal pigment epithelium (which normally expresses tyrosinase) secretes a modulatory factor, possibly L-DOPA, which regulates light adaptation in the retinal circuitry.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Variability and dark-pulse sensitivity of the sdy OKR.
Figure 2: Molecular identification of sdy/tyrosinase.
Figure 3: PTU phenocopies the light-adaptation deficit of the sdy mutation.
Figure 4: Abnormal electrophysiological light responses of the sdy retina.
Figure 5: Recovery from a light flash is disrupted in the sdy retina.
Figure 6: Recovery of sensitivity in the light is slowed down as the duration of the adapting light increases.
Figure 7: Photoreceptors function normally in sdy mutants.
Figure 8: Dark and light adaptation are out of balance in sdy mutants.

Similar content being viewed by others

Accession codes

Accessions

GenBank/EMBL/DDBJ

References

  1. Fain, G.L., Matthews, H.R., Cornwall, M.C. & Koutalos, Y. Adaptation in vertebrate photoreceptors. Physiol. Rev. 81, 117–151 (2001).

    Article  CAS  Google Scholar 

  2. Dearry, A. & Burnside, B. Dopaminergic regulation of cone retinomotor movement in isolated teleost retinas: I. Induction of cone contraction is mediated by D2 receptors. J. Neurochem. 46, 1006–1021 (1986).

    Article  CAS  Google Scholar 

  3. Wagner, H.J. & Djamgoz, M.B. Spinules: a case for retinal synaptic plasticity. Trends Neurosci. 16, 201–206 (1993).

    Article  CAS  Google Scholar 

  4. Biehlmaier, O., Neuhauss, S.C. & Kohler, K. Synaptic plasticity and functionality at the cone terminal of the developing zebrafish retina. J. Neurobiol. 56, 222–236 (2003).

    Article  CAS  Google Scholar 

  5. Witkovsky, P. Dopamine and retinal function. Doc. Ophthalmol. 108, 17–40 (2004).

    Article  Google Scholar 

  6. Djamgoz, M.B. & Wagner, H.J. Localization and function of dopamine in the adult vertebrate retina. Neurochem. Int. 20, 139–191 (1992).

    Article  CAS  Google Scholar 

  7. Dowling, J.E. & Ehinger, B. Synaptic organization of the amine-containing interplexiform cells of the goldfish and Cebus monkey retinas. Science 188, 270–273 (1975).

    Article  CAS  Google Scholar 

  8. Douglas, R.H., Wagner, H.J., Zaunreiter, M., Behrens, U.D. & Djamgoz, M.B. The effect of dopamine depletion on light-evoked and circadian retinomotor movements in the teleost retina. Vis. Neurosci. 9, 335–343 (1992).

    Article  CAS  Google Scholar 

  9. Ball, A.K., Baldridge, W.H. & Fernback, T.C. Neuromodulation of pigment movement in the RPE of normal and 6-OHDA-lesioned goldfish retinas. Vis. Neurosci. 10, 529–540 (1993).

    Article  CAS  Google Scholar 

  10. Lin, Z.S. & Yazulla, S. Depletion of retinal dopamine does not affect the ERG b-wave increment threshold function in goldfish in vivo. Vis. Neurosci. 11, 695–702 (1994).

    Article  CAS  Google Scholar 

  11. Lin, Z.S. & Yazulla, S. Depletion of retinal dopamine increases brightness perception in goldfish. Vis. Neurosci. 11, 683–693 (1994).

    Article  CAS  Google Scholar 

  12. Li, L. & Dowling, J.E. Effects of dopamine depletion on visual sensitivity of zebrafish. J. Neurosci. 20, 1893–1903 (2000).

    Article  CAS  Google Scholar 

  13. Yang, X.L., Tornqvist, K. & Dowling, J.E. Modulation of cone horizontal cell activity in the teleost fish retina. II. Role of interplexiform cells and dopamine in regulating light responsiveness. J. Neurosci. 8, 2269–2278 (1988).

    Article  CAS  Google Scholar 

  14. Wagner, H.J., Behrens, U.D., Zaunreiter, M. & Douglas, R.H. The circadian component of spinule dynamics in teleost retinal horizontal cells is dependent on the dopaminergic system. Vis. Neurosci. 9, 345–351 (1992).

    Article  CAS  Google Scholar 

  15. Yazulla, S., Lin, Z.S. & Studholme, K.M. Dopaminergic control of light-adaptive synaptic plasticity and role in goldfish visual behavior. Vision Res. 36, 4045–4057 (1996).

    Article  CAS  Google Scholar 

  16. Haffter, P. et al. Mutations affecting pigmentation and shape of the adult zebrafish. Dev. Genes Evol. 206, 260–276 (1996).

    Article  CAS  Google Scholar 

  17. Kelsh, R.N. et al. Zebrafish pigmentation mutations and the processes of neural crest development. Development 123, 369–389 (1996).

    CAS  PubMed  Google Scholar 

  18. Neuhauss, S.C. et al. Genetic disorders of vision revealed by a behavioral screen of 400 essential loci in zebrafish. J. Neurosci. 19, 8603–8615 (1999).

    Article  CAS  Google Scholar 

  19. Jeffery, G. The albino retina: an abnormality that provides insight into normal retinal development. Trends Neurosci. 20, 165–169 (1997).

    Article  CAS  Google Scholar 

  20. Easter, S.S. Jr. & Nicola, G.N. The development of vision in the zebrafish (Danio rerio). Dev. Biol. 180, 646–663 (1996).

    Article  CAS  Google Scholar 

  21. Bilotta, J., Saszik, S. & Sutherland, S.E. Rod contributions to the electroretinogram of the dark-adapted developing zebrafish. Dev. Dyn. 222, 564–570 (2001).

    Article  CAS  Google Scholar 

  22. Brockerhoff, S.E. et al. A behavioral screen for isolating zebrafish mutants with visual system defects. Proc. Natl. Acad. Sci. USA 92, 10545–10549 (1995).

    Article  CAS  Google Scholar 

  23. Roeser, T. & Baier, H. Visuomotor behaviors in larval zebrafish after GFP-guided laser ablation of the optic tectum. J. Neurosci. 23, 3726–3734 (2003).

    Article  CAS  Google Scholar 

  24. Oetting, W.S. & King, R.A. Molecular basis of albinism: mutations and polymorphisms of pigmentation genes associated with albinism. Hum. Mutat. 13, 99–115 (1999).

    Article  CAS  Google Scholar 

  25. Opitz, S., Kasmann-Kellner, B., Kaufmann, M., Schwinger, E. & Zuhlke, C. Detection of 53 novel DNA variations within the tyrosinase gene and accumulation of mutations in 17 patients with albinism. Hum. Mutat. 23, 630–631 (2004).

    Article  Google Scholar 

  26. Inagaki, H., Koga, A., Bessho, Y. & Hori, H. The tyrosinase gene from medakafish: transgenic expression rescues albino mutation. Pigment Cell Res. 11, 283–290 (1998).

    Article  CAS  Google Scholar 

  27. Van Epps, H.A., Yim, C.M., Hurley, J.B. & Brockerhoff, S.E. Investigations of photoreceptor synaptic transmission and light adaptation in the zebrafish visual mutant nrc. Invest. Ophthalmol. Vis. Sci. 42, 868–874 (2001).

    CAS  PubMed  Google Scholar 

  28. Seeliger, M.W., Rilk, A. & Neuhauss, S.C. Ganzfeld ERG in zebrafish larvae. Doc. Ophthalmol. 104, 57–68 (2002).

    Article  Google Scholar 

  29. Behrens, U.D., Douglas, R.H., Sugden, D., Davies, D.J. & Wagner, H.J. Effect of melatonin agonists and antagonists on horizontal cell spinule formation and dopamine release in a fish retina. Cell Tissue Res. 299, 299–306 (2000).

    Article  CAS  Google Scholar 

  30. Cahill, G.M. & Besharse, J.C. Resetting the circadian clock in cultured Xenopus eyecups: regulation of retinal melatonin rhythms by light and D2 dopamine receptors. J. Neurosci. 11, 2959–2971 (1991).

    Article  CAS  Google Scholar 

  31. Manglapus, M.K., Iuvone, P.M., Underwood, H., Pierce, M.E. & Barlow, R.B. Dopamine mediates circadian rhythms of rod-cone dominance in the Japanese quail retina. J. Neurosci. 19, 4132–4141 (1999).

    Article  CAS  Google Scholar 

  32. Zaunreiter, M., Brandstatter, R. & Goldschmid, A. Evidence for an endogenous clock in the retina of rainbow trout: I. Retinomotor movements, dopamine and melatonin. Neuroreport 9, 1205–1209 (1998).

    Article  CAS  Google Scholar 

  33. Wu, J., Peachey, N.S. & Marmorstein, A.D. Light-evoked responses of the mouse retinal pigment epithelium. J. Neurophysiol. 91, 1134–1142 (2004).

    Article  Google Scholar 

  34. Peirson, S.N. et al. Expression of the candidate circadian photopigment melanopsin (Opn4) in the mouse retinal pigment epithelium. Brain Res. Mol. Brain Res. 123, 132–135 (2004).

    Article  CAS  Google Scholar 

  35. Tychsen, L. & Sitaram, N. Catecholamine depletion produces irrepressible saccadic eye movements in normal humans. Ann. Neurol. 25, 444–449 (1989).

    Article  CAS  Google Scholar 

  36. Salas, C., Navarro, F., Torres, B. & Delgado-Garcia, J.M. Effects of diazepam and D-amphetamine on rhythmic pattern of eye movements in goldfish. Neuroreport 3, 131–134 (1992).

    Article  CAS  Google Scholar 

  37. Rios, M. et al. Catecholamine synthesis is mediated by tyrosinase in the absence of tyrosine hydroxylase. J. Neurosci. 19, 3519–3526 (1999).

    Article  CAS  Google Scholar 

  38. Witkovsky, P. & Shi, X.P. Slow light and dark adaptation of horizontal cells in the Xenopus retina: a role for endogenous dopamine. Vis. Neurosci. 5, 405–413 (1990).

    Article  CAS  Google Scholar 

  39. Nir, I. et al. Dysfunctional light-evoked regulation of cAMP in photoreceptors and abnormal retinal adaptation in mice lacking dopamine D4 receptors. J. Neurosci. 22, 2063–2073 (2002).

    Article  CAS  Google Scholar 

  40. Libby, R.T. et al. Modification of ocular defects in mouse developmental glaucoma models by tyrosinase. Science 299, 1578–1581 (2003).

    Article  CAS  Google Scholar 

  41. Ilia, M. & Jeffery, G. Retinal mitosis is regulated by dopa, a melanin precursor that may influence the time at which cells exit the cell cycle: analysis of patterns of cell production in pigmented and albino retinae. J. Comp. Neurol. 405, 394–405 (1999).

    Article  CAS  Google Scholar 

  42. Kubrusly, R.C. et al. L-DOPA supply to the neuro retina activates dopaminergic communication at the early stages of embryonic development. J. Neurochem. 86, 45–54 (2003).

    Article  CAS  Google Scholar 

  43. Geisler, R. et al. A radiation hybrid map of the zebrafish genome. Nat. Genet. 23, 86–89 (1999).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank J. Kay, A. Wehman, S. Taha, and M. Orger for comments on the manuscript and all members of our laboratory for discussions. We also thank A. Churchland and L. Gitlin for assistance in the initial identification of zebrafish tyrosinase. This study was supported by a NARSAD Young Investigator award and the UCSF Neuroscience training grant (P.P.-M.), a B.I.F. fellowship (T.R.), the Packard Foundation, the Sloan Foundation and the NIH (H.B.).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Herwig Baier.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Page-McCaw, P., Chung, S., Muto, A. et al. Retinal network adaptation to bright light requires tyrosinase. Nat Neurosci 7, 1329–1336 (2004). https://doi.org/10.1038/nn1344

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nn1344

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing