TY - JOUR
T1 - Pannexin 1 sustains the electrophysiological responsiveness of retinal ganglion cells
AU - Dvoriantchikova, Galina
AU - Pronin, Alexey
AU - Kurtenbach, Sarah
AU - Toychiev, Abduqodir
AU - Chou, Tsung Han
AU - Yee, Christopher W.
AU - Prindeville, Breanne
AU - Tayou, Junior
AU - Porciatti, Vittorio
AU - Sagdullaev, Botir T.
AU - Slepak, Vladlen Z.
AU - Shestopalov, Valery I.
N1 - Funding Information:
We are grateful to Drs G. Zoidl and N. Prochnow for consultations on patch clamp recordings, to Dr. E. Ivanova for advising us on retinal flat-mount immunostaining, to Drs D.W. Laird and S. Penuela for providing the anti-mPanx1 antibodies, to Dr. Hong Yu for technical assistance with PERG recordings, Dr. A. Tuzhikov for the assistance with imaging software, Dr. V. Talla for assistance with AAV2 expression vector constructs, A. Raiser for the help with the behavioral testing, J. Shestopalov for graphical art and Drs A. Hackam and A. Kurtenbach for critical reading of the manuscript. Panx1−/−/B6 mouse strain was developed by Dr. V. Dixit and provided by Genentech. This work was supported by National Institute of Health grants R01EY020535 (BTS), RO1EY018666 (VZS), R01EY021517 (VIS), the Russian Science Foundation grant N17-15-01433 (VIS), National Institute of Health center grant P30 EY014801, an unrestricted Research to Prevent Blindness and Department of Defense grant W81XWH-13-1-0048 to the Department of Ophthalmology.
Funding Information:
We are grateful to Drs G. Zoidl and N. Prochnow for consultations on patch clamp recordings, to Dr. E. Ivanova for advising us on retinal flat-mount immunostaining, to Drs D.W. Laird and S. Penuela for providing the antimPanx1 antibodies, to Dr. Hong Yu for technical assistance with PERG recordings, Dr. A. Tuzhikov for the assistance with imaging software, Dr. V. Talla for assistance with AAV2 expression vector constructs, A. Raiser for the help with the behavioral testing, J. Shestopalov for graphical art and Drs A. Hackam and A. Kurtenbach for critical reading of the manuscript. Panx1-/-/B6 mouse strain was developed by Dr. V. Dixit and provided by Genentech. This work was supported by National Institute of Health grants R01EY020535 (BTS), RO1EY018666 (VZS), R01EY021517 (VIS), the Russian Science Foundation grant N17-15-01433 (VIS), National Institute of Health center grant P30 EY014801, an unrestricted Research to Prevent Blindness and Department of Defense grant W81XWH-13-1-0048 to the Department of Ophthalmology.
Publisher Copyright:
© 2018 The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - Pannexin 1 (Panx1) forms ATP-permeable membrane channels that play a key role in purinergic signaling in the nervous system in both normal and pathological conditions. In the retina, particularly high levels of Panx1 are found in retinal ganglion cells (RGCs), but the normal physiological function in these cells remains unclear. In this study, we used patch clamp recordings in the intact inner retina to show that evoked currents characteristic of Panx1 channel activity were detected only in RGCs, particularly in the OFF-type cells. The analysis of pattern electroretinogram (PERG) recordings indicated that Panx1 contributes to the electrical output of the retina. Consistently, PERG amplitudes were significantly impaired in the eyes with targeted ablation of the Panx1 gene in RGCs. Under ocular hypertension and ischemic conditions, however, high Panx1 activity permeated cell membranes and facilitated the selective loss of RGCs or stably transfected Neuro2A cells. Our results show that high expression of the Panx1 channel in RGCs is essential for visual function in the inner retina but makes these cells highly sensitive to mechanical and ischemic stresses. These findings are relevant to the pathophysiology of retinal disorders induced by increased intraocular pressure, such as glaucoma.
AB - Pannexin 1 (Panx1) forms ATP-permeable membrane channels that play a key role in purinergic signaling in the nervous system in both normal and pathological conditions. In the retina, particularly high levels of Panx1 are found in retinal ganglion cells (RGCs), but the normal physiological function in these cells remains unclear. In this study, we used patch clamp recordings in the intact inner retina to show that evoked currents characteristic of Panx1 channel activity were detected only in RGCs, particularly in the OFF-type cells. The analysis of pattern electroretinogram (PERG) recordings indicated that Panx1 contributes to the electrical output of the retina. Consistently, PERG amplitudes were significantly impaired in the eyes with targeted ablation of the Panx1 gene in RGCs. Under ocular hypertension and ischemic conditions, however, high Panx1 activity permeated cell membranes and facilitated the selective loss of RGCs or stably transfected Neuro2A cells. Our results show that high expression of the Panx1 channel in RGCs is essential for visual function in the inner retina but makes these cells highly sensitive to mechanical and ischemic stresses. These findings are relevant to the pathophysiology of retinal disorders induced by increased intraocular pressure, such as glaucoma.
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U2 - 10.1038/s41598-018-23894-2
DO - 10.1038/s41598-018-23894-2
M3 - Article
C2 - 29643381
AN - SCOPUS:85045381662
VL - 8
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 5797
ER -