Multielectrode Array Recording of Mouse Retinas Transplanted with Stem Cell-Derived Retinal Sheets

  • Hung-Ya TuEmail author
  • Take Matsuyama
Part of the Methods in Molecular Biology book series (MIMB, volume 2092)


Retinal multielectrode array (MEA) recording allows us to examine the action potentials of retinal ganglion cells and field potentials of photoreceptors and bipolar cells. In addition to studying the retinal circuitry, it has become one of the standard examination tools for the characterization of stem cell-derived retinal transplantation in degenerated retinas. Besides the detection of responses to simple light stimulation, it is also necessary to consider the spatial correlation of the graft and the electrodes, in order to unbiasedly reveal the locally reconstructed retinal circuitry after transplantation. Here, we introduce our newly developed protocol of MEA recording and analysis that may serve as a standard for evaluating transplanted retinas.

Key words

Multielectrode array (MEA) Micro-electroretinogram (mERG) Spike sorting iPS/ES cell-derived 3D retina Retinal transplantation Metabotropic glutamate receptor type 6 (mGluR6) L-AP4 ON bipolar cells Retinal ganglion cells (RGCs) Bayesian inference 



We would like to thank the Laboratory for Retinal Regeneration in RIKEN, Japan, especially for the retinal transplantation team led by Dr. Michiko Mandai. This methodology would not have been developed without the generous support from the team members.


  1. 1.
    Elstrott J, Anishchenko A, Greschner M, Sher A, Litke AM, Chichilnisky EJ, Feller MB (2008) Direction selectivity in the retina is established independent of visual experience and cholinergic retinal waves. Neuron 58(4):499–506. Scholar
  2. 2.
    Field GD, Gauthier JL, Sher A, Greschner M, Machado TA, Jepson LH, Shlens J, Gunning DE, Mathieson K, Dabrowski W, Paninski L, Litke AM, Chichilnisky EJ (2010) Functional connectivity in the retina at the resolution of photoreceptors. Nature 467(7316):673–677. Scholar
  3. 3.
    Farajian R, Pan F, Akopian A, Volgyi B, Bloomfield SA (2011) Masked excitatory crosstalk between the ON and OFF visual pathways in the mammalian retina. J Physiol 589(Pt 18):4473–4489. Scholar
  4. 4.
    Tu DC, Zhang D, Demas J, Slutsky EB, Provencio I, Holy TE, Van Gelder RN (2005) Physiologic diversity and development of intrinsically photosensitive retinal ganglion cells. Neuron 48(6):987–999. Scholar
  5. 5.
    Firth SI, Wang CT, Feller MB (2005) Retinal waves: mechanisms and function in visual system development. Cell Calcium 37(5):425–432. Scholar
  6. 6.
    Wong RO (1999) Retinal waves and visual system development. Annu Rev Neurosci 22:29–47. Scholar
  7. 7.
    Wong RO, Meister M, Shatz CJ (1993) Transient period of correlated bursting activity during development of the mammalian retina. Neuron 11(5):923–938CrossRefGoogle Scholar
  8. 8.
    Stasheff SF (2008) Emergence of sustained spontaneous hyperactivity and temporary preservation of OFF responses in ganglion cells of the retinal degeneration (rd1) mouse. J Neurophysiol 99(3):1408–1421. Scholar
  9. 9.
    Barrett JM, Degenaar P, Sernagor E (2015) Blockade of pathological retinal ganglion cell hyperactivity improves optogenetically evoked light responses in rd1 mice. Front Cell Neurosci 9:330. Scholar
  10. 10.
    Fujii M, Sunagawa GA, Kondo M, Takahashi M, Mandai M (2016) Evaluation of micro electroretinograms recorded with multiple electrode array to assess focal retinal function. Sci Rep 6:30719. Scholar
  11. 11.
    Iraha S, Tu HY, Yamasaki S, Kagawa T, Goto M, Takahashi R, Watanabe T, Sugita S, Yonemura S, Sunagawa GA, Matsuyama T, Fujii M, Kuwahara A, Kishino A, Koide N, Eiraku M, Tanihara H, Takahashi M, Mandai M (2018) Establishment of immunodeficient retinal degeneration model mice and functional maturation of human ESC-derived retinal sheets after transplantation. Stem Cell Reports 10(3):1059–1074. Scholar
  12. 12.
    Tu HY, Watanabe T, Shirai H, Yamasaki S, Kinoshita M, Matsushita K, Hashiguchi T, Onoe H, Matsuyama T, Kuwahara A, Kishino A, Kimura T, Eiraku M, Suzuma K, Kitaoka T, Takahashi M, Mandai M (2018) Medium- to long-term survival and functional examination of human iPSC-derived retinas in rat and primate models of retinal degeneration. EBioMedicine. Scholar
  13. 13.
    Assawachananont J, Mandai M, Okamoto S, Yamada C, Eiraku M, Yonemura S, Sasai Y, Takahashi M (2014) Transplantation of embryonic and induced pluripotent stem cell-derived 3D retinal sheets into retinal degenerative mice. Stem Cell Reports 2(5):662–674. Scholar
  14. 14.
    Mandai M, Fujii M, Hashiguchi T, Sunagawa GA, Ito SI, Sun J, Kaneko J, Sho J, Yamada C, Takahashi M (2017) iPSC-derived retina transplants improve vision in rd1 end-stage retinal-degeneration mice. Stem Cell Reports 8(1):69–83. Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2020

Authors and Affiliations

  1. 1.Laboratory for Retinal RegenerationCenter for Biosystems Dynamics Research, RIKENKobeJapan

Personalised recommendations