The role of reactive gliosis of Müller cells in retinal ischemia
Augenheilkunde
Zusammenfassung der Projektergebnisse
During diseases and injuries of the nervous system, glial cells undergo a process referred to as reactive gliosis. Although morphological and functional alterations of gliotic cells have been described, the regulation of this process is not well understood. The aim of the presented project was to learn more about the involvement of certain receptors, ion channels and other proteins in reactive gliosis by using the retinal Müller glial cell as a model. Transient retinal ischemia was induced in mice by increasing the intraocular pressure for 90 min, afterwards, the animals survived for 1-7 days. It has been shown before that Müller cells from postischemic retinae are characterized by a reduced K+ conductance, by a disturbed volume regulation and by an increase in the expression of intermediate filament proteins. Now, Müller cells were investigated in genetically altered mouse strains. Mice were used that did not express the nucleotide receptor P2Y1, the intracellular IP3R2 receptor, the intermediate filament proteins GFAP and vimentin, or the leukemia inhibiting factor (LIF). Moreover, transgenic dnSNARE mice were used that express the dnSNARE domain specifically in glial cells, thus inhibiting vesicle-mediated exocytosis. It has been found that the lack of the P2Y1 or of the IP3R2 receptors cause a less severe downregulation of Müller cell inward currents after ischemia. However, apoptosis-mediated degeneration of photoreceptors in the postischemic retina of P2Y1-/- and IP3R2-/- mice was increased compared to the wild type. In contrast, the lack of P2Y1 improved the survival of amacrine cells in the inner retina after ischemia. Using a PCR array, a number of differences in the gene expression between the retina of wild type and P2Y1-/- mice was observed, regarding the untreated as well as the postischemic retina. Using an enzymatic assay, the release of glutamate from single cells could be detected. The amount of released glutamate was decreased in Müller cells from dnSNARE mice, demonstrating that Müller cells are capable of glutamate exocytosis. After transient retinal ischemia, the number of surviving cells was higher in postischemic retinae of dnSNARE mice, suggesting that glial glutamate may contribute to neuronal degeneration. It was demonstrated that Müller cells of GFAP-/-/Vim-/- mice have inward currents of smaller amplitudes than wild type mice in the untreated retina, whereas the amplitudes were decreased to similar values in both strains after ischemia.
Projektbezogene Publikationen (Auswahl)
- Differential effects of P2Y1 deletion on glial activation and survival of photoreceptors and amacrine cells in the ischemic mouse retina. Cell Death Dis 2014,5:e1353
Pannicke T, Frommherz I, Biedermann B, Wagner L, Sauer K, Ulbricht E, Härtig W, Krügel U, Ueberham U, Arendt T, Illes P, Bringmann A, Reichenbach A, Grosche A
(Siehe online unter https://doi.org/10.1038/cddis.2014.317) - Glutamate release from satellite glial cells of the murine trigeminal ganglion. Neurosci Lett 2014,578:143-147
Wagner L, Warwick RA, Pannicke T, Reichenbach A, Grosche A, Hanani M
(Siehe online unter https://doi.org/10.1016/j.neulet.2014.06.047) - Retinal functional alterations in mice lacking intermediate filament proteins GFAP and vimentin. FASEB J 2015,29:4815-4828
Wunderlich KA, Tanimoto N, Grosche A, Zrenner E, Pekny M, Reichenbach A, Seeliger MW, Pannicke T, Perez MT
(Siehe online unter https://doi.org/10.1096/fj.15-272963)
