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- Title
Impaired Purinergic Regulation of the Glial (Müller) Cell Volume in the Retina of Transgenic Rats Expressing Defective Polycystin-2.
- Authors
Vogler, Stefanie; Pannicke, Thomas; Hollborn, Margrit; Kolibabka, Matthias; Wiedemann, Peter; Reichenbach, Andreas; Hammes, Hans-Peter; Bringmann, Andreas
- Abstract
Retinal glial (Müller) cells possess an endogenous purinergic signal transduction cascade which normally prevents cellular swelling in osmotic stress. The cascade can be activated by osmotic or glutamate receptor-dependent ATP release. We determined whether activation of this cascade is altered in Müller cells of transgenic rats that suffer from a slow photoreceptor degeneration due to the expression of a truncated human cilia gene polycystin-2 (CMV-PKD2 HA). Age-matched Sprague-Dawley rats served as control. Retinal slices were superfused with a hypoosmotic solution (60 % osmolarity). Müller cells in retinas of PKD2 rats swelled immediately in hypoosmotic stress; this was not observed in control retinas. Pharmacological blockade of P2Y or adenosine A receptors induced osmotic swelling of Müller cells from control rats. The swelling induced by the P2Y receptor antagonist was mediated by induction of oxidative-nitrosative stress, mitochondrial dysfunction, production of inflammatory lipid mediators, and a sodium influx from the extracellular space. Exogenous VEGF or glutamate prevented the hypoosmotic swelling of Müller cells from PKD2 rats; this effect was mediated by activation of the purinergic signaling cascade. In neuroretinas of PKD2 rats, the gene expression levels of P2Y and A receptors, pannexin-1, connexin 45, NTPDases 1 and 2, and various subtypes of nucleoside transporters are elevated compared to control. The data may suggest that the osmotic swelling of Müller cells from PKD2 rats is caused by an abrogation of the osmotic ATP release while the glutamate-induced ATP release is functional. In the normal retina, ATP release and autocrine P2Y receptor activation serve to inhibit the induction of oxidative-nitrosative stress, mitochondrial dysfunction, and production of inflammatory lipid mediators, which otherwise will induce a sodium influx and cytotoxic Müller cell swelling under anisoosmotic conditions. Purinergic receptors may represent a target for the protection of retinal glial cells from mitochondrial oxidative stress.
- Subjects
RETINA analysis; PURINERGIC receptors; GENETIC regulation; CELL size; POLYCYSTINS; GENE expression; CELLULAR signal transduction; LABORATORY rats
- Publication
Neurochemical Research, 2016, Vol 41, Issue 7, p1784
- ISSN
0364-3190
- Publication type
Article
- DOI
10.1007/s11064-016-1894-0