P2X receptor modulates visual information processing in the mouse retina

• Project/Area Number: 17K16990
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Ophthalmology
• Research Institution: Nippon Medical School
• Principal Investigator: Ishii Toshiyuki 日本医科大学, 医学部, 講師 (10643140)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: P2X受容体 / 網膜 / 視覚 / 網膜電図 / ATP / 網膜神経節細胞 / P2X3 / retina

Outline of Final Research Achievements

ATP acts as a neurotransmitter in the nervous system. All subtypes of P2X receptors (P2X1 - P2X7) exist in the mouse retina at the immunohistochemical level, and PPADS, a non-selective P2 receptor antagonist, modulates the responses of bipolar cells to light flash and the firing pattern of retinal ganglion cells (RGCs). However, the types of P2X receptors contributing the signal processing in the retina have not been well elucidated. In the present study, we focused on P2X3 receptors and tested whether P2X3 receptors are physiologically functioning by the electroretinogram and multi electrode array. Intravitreal injection of A317491, an antagonist of P2X3 receptor, had no effects on the amplitude of a and b-wave whereas the amplitude of oscillatory potentials was significantly decreased. In addition, application of A317491 modulated the firing rate of RGCs. These results suggest that the P2X3 receptors physiologically work for the signal processing in the mouse retina.

Academic Significance and Societal Importance of the Research Achievements

本研究を通じ、網膜内視覚情報処理にP2X3受容体が関与していることが明らかとなった。P2X3受容体の機能異常は、代償が起こらない限り視覚障害を導くものと推測される。そのため、P2X3受容体は、mGluR6受容体やTRPM1受容体と並び、先天性停止性夜盲症などといった先天性疾患に関わる新たな原因分子の一つとなる可能性が考えられる。

Research Products

• [Journal Article] Variation in the Phenotype of Photosensitive Cells Produced from Human Fibroblast Cell Lines (2018)
  • Author(s): Ishii, T., Yin C., Seko Y., Umezawa A., and Kaneda M.
  • Journal Title: Journal of Nippon Medical School Volume: 85 Issue: 2 Pages: 110-116
  • DOI: 10.1272/jnms.2018_85-17
  • NAID: 130006731160
  • ISSN: 1345-4676, 1347-3409
  • Year and Date: 2018-04-15
  • Peer Reviewed
• [Journal Article] Opposing Roles of Peripherally-Derived CD4+ αβ Regulatory and γδ T Cells in the Pathogenesis of Intractable Pediatric Epilepsy. (2018)
  • Author(s): Xu D., Robinson A., Ishii T., Duncan D., Alden T., Goings G., Ifergan I., Podojil J., Penaloza-MacMaster P., Kearney J., Swanson G., Miller S., and Koh S.
  • Journal Title: The Journal of Experimental Medicine Volume: 215 Issue: 4 Pages: 1169-1186
  • DOI: 10.1084/jem.20171285
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Novel channel-mediated choline transport in cholinergic neurons of the mouse retina. (2017)
  • Author(s): Ishii T, Homma K, Mano A, Akagi T, Shigematsu Y, Shimoda Y, Inoue H, Kakinuma Y, Kaneda M.
  • Journal Title: J Neurophysiol. Volume: 118 Issue: 4 Pages: 1952-1961
  • DOI: 10.1152/jn.00506.2016
  • Peer Reviewed
• [Journal Article] Excitatory synaptic input to hilar mossy cells under basal and hyperexcitable conditions. (2017)
  • Author(s): Hedrick T.P., Nobis W.P., Foote K.M., Ishii T., Chetkovich D.M., and Swanson G.T.
  • Journal Title: eNeuro Volume: 4 Issue: 6 Pages: ENEURO.0364-17.2017
  • DOI: 10.1523/eneuro.0364-17.2017
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Physiological contribution of P2X receptors in postreceptoral signal processing in the mouse retina. Neurosci. Res. (2017)
  • Author(s): Ichinohe S., Ishii T., Takahashi H., and Kaneda M.
  • Journal Title: Neuroscience Research Volume: 115 Pages: 5-12
  • DOI: 10.1016/j.neures.2016.09.012
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Functional characterization of AMPA receptor positive allosteric modulators PF-04958242 and LY-451395. (2018)
  • Author(s): Ishii T., Stolz J.R., and Swanson G.T.
  • Organizer: World Congress of Basic and Clinical Pharmacology (WCP2018)
  • Int'l Joint Research
• [Presentation] Physiological characterization of AMPA receptor positive allosteric modulators PF-04958242 and LY-451395. (2018)
  • Author(s): Ishii T., Stolz J.R., and Swanson G.T.
  • Organizer: 日本神経科学大会
• [Presentation] Contribution of P2X3 receptor to light responses in the mouse retina. (2017)
  • Author(s): Ishii T., Ichinohe S., Suzuki C., Takahashi H., and Kaneda M.
  • Organizer: 日本神経科学大会
• [Presentation] Comparative studies of AMPA receptor positive allosteric modulators PF-04958242 and PF-04531686. (2017)
  • Author(s): Stolz J.R., Ishii T., and Swanson G.T.
  • Organizer: Experimental Biology 2017 (ASPET)
  • Int'l Joint Research