July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Functional Piezo1 Mechanosensitive Ion Channels in Retinal Ganglion Cells
Author Affiliations & Notes
  • Taylor Friemel
    The Pennsylvania State College of Medicine, Hershey, Pennsylvania, United States
  • Salvatore L Stella
    The Pennsylvania State College of Medicine, Hershey, Pennsylvania, United States
  • Footnotes
    Commercial Relationships   Taylor Friemel, None; Salvatore Stella, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 5288. doi:
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      Taylor Friemel, Salvatore L Stella; Functional Piezo1 Mechanosensitive Ion Channels in Retinal Ganglion Cells. Invest. Ophthalmol. Vis. Sci. 2019;60(9):5288.

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

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Purpose : Piezo1 mechanosensitive ion channels have been identified in a variety of tissues, and play an important role in mechanotransduction in vertebrates. The goal of our present study is to characterize the localization and functionality of Piezo1 channels in zebrafish and mammalian retina.

Methods : Activation of Piezo1 mechanosensitive channels was probed with the chemical channel activator, Yoda1. Intracellular Ca2+ signals were measured using either fluo-4 pentapotassium salt injected into the optic nerve of rodents or a genetically-encoded Ca2+ indicator targeted to retinal ganglion cells (RGCs) in Tg(elavl3: GCaMP6f) zebrafish. Confirmation of RGCs was identified by backfilling the optic nerve head with Texas Red Hydrazide. Antibodies targeted to Piezo1 channels were used for both immunoblotting and immunohistochemical localization on retinal sections and wholemounts. All imaging was performed using confocal microscopy and Ca2+ imaging data were normalized to the change in fluorescence intensity over baseline (ΔF/F=(F-Fo)/Fo).

Results : Ca2+ imaging experiments in RGCs revealed that Yoda1 evoked a dose-dependent increase in Ca2+ following activation of Piezo1 channels with an EC50 of 76.2µM in RGCs that was blocked by the application of the mechanosensitive channel antagonist GsMTx-4. Ca2+ was derived exclusively from the outside of the cell, thus Yoda1-evoked Ca2+ responses were largely dependent on Ca2+ influx. The chelation of extracellular Ca2+ with EGTA (5mM) dramatically reduced the Yoda1-evoked response, while the depletion of intracellular Ca2+ stores using BHQ (25µM) did not. However, Ca2+-chelating conditions did not consistently abolish the responses. Immunoblotting demonstrated the presence of a large molecular weight band at 260kD from retina and immunolabeling showed strong immunoreactivity in both RGCs and outer retinal neurons in both zebrafish and rodent retinas.

Conclusions : This study demonstrates the first functional characterization of Piezo1 channels in vertebrate retina, suggesting the possibility that these channels could influence Ca2+ driven apoptosis in RGCs. Moreover, it is possible that neurodegenerative conditions like glaucoma, where RGCs are impacted by elevated intraocular pressure, could contribute to the triggering of Ca2+ mediated cell death through Piezo1 channel activation.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.


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