title: Experimental dispase-induced retinopathy causes up-regulation of P2Y receptor-mediated calcium responses in Müller glial cells.
abstract: During proliferative vitreoretinopathy (PVR) Müller glial cells show an up-regulation of their responsiveness to extracellular adenosine 5'-triphosphate (ATP). In the present study, we investigated if such a glial cell response is also a feature for other retinopathies besides PVR. To this aim, the proteolytic enzyme, dispase (0.1 U), was injected into the vitreous of rabbit eyes. After 3 weeks, a distinct retinopathy had developed which showed no signs of PVR. The retinopathy was characterized by strong alterations of the retinal vasculature in the medullary rays, by photoreceptor degeneration, retinal atrophy, and activation of microglial cells. Müller cells became reactive, as indicated by up-regulation of glial fibrillary acidic protein immunoreactivity and by hypertrophy involving subretinal fibrosis. Müller cell reactivity was also evidenced electrophysiologically by a down-regulation of their inwardly rectifying potassium currents and by an up-regulation of their responsiveness to extracellular ATP. Significantly more Müller cells from dispase-treated eyes showed ATP-evoked calcium (83%) and current responses (69%) when compared with cells from control eyes (13 and 9%, respectively). The results indicate that increased responsiveness to extracellular ATP may be a more general feature of Müller cell gliosis, and is also observed in retinopathies besides PVR.
authors.affiliation: Department of Neurophysiology, Paul Flechsig Institute for Brain Research, University of Leipzig, Leipzig, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Francke
authors.forename: S
authors.initials: S
authors.lastname: Uhlmann
authors.forename: T
authors.initials: T
authors.lastname: Pannicke
authors.forename: I
authors.initials: I
authors.lastname: Goczalik
authors.forename: O
authors.initials: O
authors.lastname: Uckermann
authors.forename: M
authors.initials: M
authors.lastname: Weick
authors.forename: W
authors.initials: W
authors.lastname: Härtig
authors.forename: P
authors.initials: P
authors.lastname: Wiedemann
authors.forename: A
authors.initials: A
authors.lastname: Reichenbach
authors.forename: A
authors.initials: A
authors.lastname: Bringmann
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004594:Electrophysiology; D010450:Endopeptidases / Q000633:toxicity; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008297:Male; D008564:Membrane Potentials; D008856:Microscopy, Fluorescence; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism; D011817:Rabbits; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D012164:Retinal Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation
chemical_list: D005904:Glial Fibrillary Acidic Protein; D051036:Large-Conductance Calcium-Activated Potassium Channels; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D018048:Receptors, Purinergic P2; D000255:Adenosine Triphosphate; D010450:Endopeptidases; C023139:dispase; D011188:Potassium; D002118:Calcium