May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Stimulation of P2X7 Receptor Kills Rat Retinal Ganglion Cells in vivo
Author Affiliations & Notes
  • H. Hu
    University of Pennsylvania, Philadelphia, Pennsylvania
    Ophthalmology,
    Zhongshan Ophthalmic Center, Guangzhou, China
  • W. Lu
    University of Pennsylvania, Philadelphia, Pennsylvania
    Physiology,
  • A. M. Laties
    University of Pennsylvania, Philadelphia, Pennsylvania
    Ophthalmology,
  • C. H. Mitchell
    University of Pennsylvania, Philadelphia, Pennsylvania
    Physiology,
  • Footnotes
    Commercial Relationships  H. Hu, None; W. Lu, None; A.M. Laties, None; C.H. Mitchell, None.
  • Footnotes
    Support  EY015537, EY013434, The Jody Sack Fund, Research to Prevent Blindness, the Paul and Evanina Bell Mackall Foundation Trust
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 2063. doi:https://doi.org/
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    • Get Citation

      H. Hu, W. Lu, A. M. Laties, C. H. Mitchell; Stimulation of P2X7 Receptor Kills Rat Retinal Ganglion Cells in vivo. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2063. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : Stimulation of the P2X7 receptor can lead to the death of many cell types. We have previously demonstrated that activation of the P2X7 receptor can elevate intracellular calcium and kill rat retinal ganglion cells that have been isolated from the eye. However, the presence of glia and other cells in the intact eye may alter the lethal effects in vivo. We ask here whether stimulation of the P2X7 receptor can kill retinal ganglion cells in vivo, and whether the NMDA receptor is involved as found in isolated cells.

Methods: : Compounds were injected into the nasal region of the vitreous chamber of Long Evans rats, PD 14-26. Ganglion cells were labeled by injecting aminostibamabine into the superior colliculus 2-3 days later. The effect on ganglion cell survival was determined by counting the number of fluorescence cells 2-3 days after the labeling. All animals were handled in accordance with the ARVO guidelines.

Results: : Intravitreal injection of the P2X7 receptor agonist BzATP significantly reduced the number of ganglion cells as compared to animals injected with saline solution. Cell loss was localized to the injection point, consistent with limited diffusion in the restricted vitreal space. This death of retinal ganglion cells was prevented by coinjection of the specific P2X7 antagonist brilliant blue G, confirming cell death was mediated by the P2X7 receptor. The loss of ganglion cells following activation of the P2X7 receptor was also prevented by the NMDA antagonist MK 801. In no case did intraocular pressure go up.

Conclusions: : Stimulation of the P2X7 receptor can kill retinal ganglion cells in vivo. Activation of the NMDA receptor appears to be downstream of P2X7 receptor activation, consistent with our findings in isolated ganglion cells. These observations suggest that situations leading to increased extracellular ATP, possibly including elevations in intraocular pressure, may lead to the loss of retinal ganglion cells in vivo.

Keywords: ganglion cells • receptors: pharmacology/physiology • adenosine 
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