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H Kawamura, T Sugiyama, DM Wu, DG Puro; Expression of functional P2X7 purinergic receptors in the retinal microvasculature. . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3698.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose:Retinal blood flow is regulated by locally synthesized molecules. A putative vasoactive signal in the retina is extracellular ATP, which is released by the glial cells ensheathing retinal vessels and is elevated at sites of cell injury and platelet activation. Here, we began to characterize the mechanisms by which ATP regulates retinal microvascular physiology. Methods:We used the perforated-patch technique to record whole-cell currents in pericytes located on freshly isolated rat retinal microvessels. Simultaneous dual recordings permitted quantification of electrotonic transmission within microvessels. Uptake of the fluorescent dye, YO-PRO-1, monitored the formation of membrane pores. We also performed immunocytochemistry using P2X7 receptor antibodies. Results:Retinal microvessels were immunoreactive to P2X7 receptor antibodies. With exposure to ATP, a large transient increase in a depolarizing current was detected in 100% of the sampled pericytes. Subsequently, cell-to-cell communication in the microvessels was profoundly decreased. These effects were mimicked by the P2X7 agonist, Bz-ATP, and prevented by oxidized ATP, a blocker of P2X7 receptors. As with cloned P2X7 receptors, we found in retinal microvessels that divalent cations inhibited the effects of Bz-ATP. Because P2X7 receptors can form membrane pores that are permeable to molecules of < 900 MW, we assessed the uptake of the normally impermeant dye, YO-PRO-1 (629 daltons) and found that Bz-ATP rapidly permeablized microvascular cells. Conclusion:Based on our electrophysiological, immunocytochemical and dye uptake studies, we conclude that rat retinal microvessels express P2X7 receptors. Their activation profoundly affects the physiology of individual microvascular cells and also significantly alters the multicellular functional organization of the retinal microvasculature.
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