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Abstract
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.
Highlights
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
Using a targeted gene knockout approach, we found a correlation between high Panx[1] expression, channel activity and an increased pattern electroretinogram (PERG) amplitude in retinal ganglion cells (RGCs), which provided evidence for the essential role of Panx[1] in normal RGCs
High levels of Panx[1] expression are essential for the normal activity of functionally specialized RGCs, as they contribute to the electrical output needed to maintain PERG responsiveness
Summary
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. Our results show that high expression of the Panx[1] 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. Physiological experiments using in vivo and in vitro microchip-mediated electroretinogram (ERG) recordings from the inner retina have shown reduced amplitudes of a- and b-waves under scotopic conditions in Panx1-null retinas[15] These results suggested that Panx[1] function in the retina may involve photoreceptor, bipolar cell, or RGC function; the data generated by this technique cannot be directly attributed to RGC function. Whether other voltage-gated channels, Panx[1], contribute to the PERG responses remains unknown
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