title: Effects of IP3R2 Receptor Deletion in the Ischemic Mouse Retina.
abstract: Glial cells in the diseased nervous system undergo a process known as reactive gliosis. Gliosis of retinal Müller glial cells is characterized by an upregulation of glial fibrillary acidic protein and frequently by a reduction of inward K(+) current amplitudes. Purinergic signaling is assumed to be involved in gliotic processes. As previously shown, lack of the nucleotide receptor P2Y1 leads to an altered regulation of K(+) currents in Müller cells of the ischemic retina. Here, we asked first whether this effect is mediated by the IP3 receptor subtype 2 (IP3R2) known as the major downstream signaling target of P2Y1 in Müller cells. The second question was whether lack of IP3R2 affects neuronal survival in the control and ischemic retina. Ischemia was induced in wild type and IP3R2-deficient (IP 3 R2 (-/-)) mice by transient elevation of the intraocular pressure. Immunostaining and TUNEL labelling were used to quantify neuronal cell loss. The downregulation of inward K(+) currents in Müller cells from ischemic IP 3 R2 (-/-) retinae was less strong than in wild type animals. The reduction of the number of cells in the ganglion cell layer and of calretinin- and calbindin-positive cells 7 days after ischemia was similar in wild type and IP 3 R2 (-/-) mice. However, IP3R2 deficiency led to an increased number of TUNEL-positive cells in the outer nuclear layer at 1 day and to an enhanced postischemic loss of photoreceptors 7 days after ischemia. This implies that IP3R2 is involved in some but not all aspects of signaling in Müller cells after an ischemic insult.
authors.affiliation: Paul-Flechsig-Institut für Hirnforschung, Universität Leipzig, Leipzig, Germany.
authors.forename: Lysann
authors.initials: L
authors.lastname: Wagner
authors.affiliation: Paul-Flechsig-Institut für Hirnforschung, Universität Leipzig, Leipzig, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Pannicke
authors.affiliation: Paul-Flechsig-Institut für Hirnforschung, Universität Leipzig, Leipzig, Germany.
authors.forename: Ina
authors.initials: I
authors.lastname: Frommherz
authors.affiliation: Paul-Flechsig-Institut für Hirnforschung, Universität Leipzig, Leipzig, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Sauer
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, CA, USA.
authors.forename: Ju
authors.initials: J
authors.lastname: Chen
authors.affiliation: Institut für Humangenetik, Universität Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany. Antje.Grosche@klinik.uni-regensburg.de.
authors.forename: Antje
authors.initials: A
authors.lastname: Grosche
mesh_terms: D000818:Animals; D002452:Cell Count; D063928:Ependymoglial Cells / Q000473:pathology; D005911:Gliosis / Q000473:pathology; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000235:genetics*; D007511:Ischemia / Q000473:pathology*; D018345:Mice, Knockout; D009474:Neurons / Q000473:pathology; D012160:Retina / Q000473:pathology*
chemical_list: D053496:Inositol 1,4,5-Trisphosphate Receptors; C580990:Ip3r2 protein, mouse
keywords: Glia; IP3R2; Ischemia; Mouse; P2Y1; Retina