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Aleksandra Polosukhina, Andy Noblet, Ivan Tochitsky, Richard H. Kramer; Changes In P2X Receptor Activity During Retinal Degeneration. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6541.
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P2X7, P2X4, and P2X2 receptors have been found to play vital role in inflammation, perception of pain, and apoptosis, thus possibly contributing to retinal ganglion cell death during retinal degeneration. The aim of this study was to assess the changes in activity of these receptors in retinal cells during the progression of retinal degeneration using a novel photosensitive reporter (QAQ).
QAQ enters through open P2X receptors, and silences the affected cells in a light reversible manner. By recording the activity of RGC cells in different wavelengths of light we assessed the amount of intracellular QAQ, which serves as a cumulative reporter of the P2X receptor activity. To determine whether P2X receptors were expressed in the rd1 mouse retinas, we extracted the retinas and directly treated them with QAQ and 2' and 3'-O-(4-benzoylbenzoyl)-ATP (bzATP, a potent P2X receptor agonist). To assess the activity of the P2X receptors, the eyes from rd1 mice (6 and 3 month old) were injected with QAQ; the retinas were then extracted and placed on the multielectrode array (MEA).
We found that application of bzATP did not induce QAQ loading in 3 month old mice while a high amount of QAQ loading was observed in 6 month old mice after bzATP application. Thus, 6 month old mice showed a significant increase in firing rate in response to light (p < 0.001). Additionally, we found that in in-vivo experiments QAQ loading was only observed in 6 month old mice, showing a significant firing rate increase in response to light (p < 0.001).
The in-vivo experiments suggest that P2X receptors become more active in the later stages of retinal degeneration, allowing large molecules like QAQ enter retinal cells. Additionally, the ex-vivo experiments with direct application of bzATP and QAQ suggest that P2X receptors are more active in older rd1 mice.
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