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Upregulation of P2X₇ Receptor Currents in Müller Glial Cells during Proliferative Vitreoretinopathy

¹ From the Department of Neurophysiology, Paul Flechsig Institute of Brain Research, and the ² Department of Ophthalmology, Eye Hospital, University of Leipzig, Germany.

PURPOSE. Müller glial cells from the human retina express purinergic P2X₇ receptors. Because extracellular adenosine triphosphate (ATP) is assumed to be a mediator of the induction or maintenance of gliosis, this study was undertaken to determine whether the expression of these receptors is different in human Müller cells obtained from retinas of healthy donors and of patients with choroidal melanoma and proliferative vitreoretinopathy (PVR).

METHODS. Human Müller cells were enzymatically isolated from donor retinas, and whole-cell patch-clamp recordings were made to characterize the density of the P2X₇ currents and the activation of currents through Ca²⁺-activated K⁺ channels of big conductance (I_BK) that reflects the increase of the intracellular Ca²⁺ concentration.

RESULTS. Stimulation by external ATP or by benzoylbenzoyl ATP (BzATP) evoked both release of Ca²⁺ from thapsigargin-sensitive intracellular stores and opening of Ca²⁺-permeable P2X₇ channels. These responses caused transient and sustained increases in I_BK. In Müller cells from patients with PVR, the mean density of the BzATP-evoked cation currents was significantly greater compared with cells from healthy donors. As a consequence, such cells displayed an enlarged I_BK during application of purinergic agonists. ATP and BzATP increased the DNA synthesis rate of cultured cells. This effect could be reversed by blocking the I_BK.

CONCLUSIONS. The increased density of P2X₇ receptor channels may permit a higher level of entry of extracellular Ca²⁺ into cells from patients with PVR. Enhanced Ca²⁺ entry and the subsequent stronger activation of I_BK may contribute to the induction or maintenance of proliferative activity in gliotic Müller cells during PVR.

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