Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 5 de 5
Filter
Add more filters










Database
Language
Publication year range
1.
Neurosci Lett ; 670: 69-74, 2018 03 23.
Article in English | MEDLINE | ID: mdl-29391217

ABSTRACT

Leukemia inhibitory factor (LIF) is a cytokine that exerts different effects in the nervous system. It is involved in neuronal injuries and diseases and is assumed to be neuroprotective and to regulate reactive gliosis. In LIF-deficient (LIF-/-) mice, expression of glial fibrillary acidic protein in retinal Müller glial cells as a hallmark of reactive gliosis is suppressed during retinal degenerations. Here, we detected expression of LIF and its receptors in Müller cells of the murine retina. Moreover, electrophysiological alterations of Müller cells 7 days after transient retinal ischemia were studied by the patch-clamp technique. The amplitude of inward currents in Müller cells from the postischemic retina was reduced to 51% in wild type and to 70% in LIF-/- mice. This demonstrates that decrease of inward currents takes place in reactive Müller cells even in the absence of LIF.


Subject(s)
Ependymoglial Cells/physiology , Ischemia/physiopathology , Leukemia Inhibitory Factor/metabolism , Retina/physiopathology , Retinal Vessels/physiopathology , Animals , Ependymoglial Cells/metabolism , Ependymoglial Cells/pathology , Ischemia/metabolism , Ischemia/pathology , Leukemia Inhibitory Factor/genetics , Membrane Potentials/physiology , Mice , Mice, Knockout , Retina/metabolism , Retina/pathology , Retinal Vessels/metabolism , Retinal Vessels/pathology
2.
Glia ; 65(7): 1059-1071, 2017 07.
Article in English | MEDLINE | ID: mdl-28370368

ABSTRACT

Nervous tissue is characterized by a tight structural association between glial cells and neurons. It is well known that glial cells support neuronal functions, but their role under pathologic conditions is less well understood. Here, we addressed this question in vivo using an experimental model of retinal ischemia and transgenic mice for glia-specific inhibition of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)-dependent exocytosis. Transgene expression reduced glutamate, but not ATP release from single Müller cells, impaired glial volume regulation under normal conditions and reduced neuronal dysfunction and death in the inner retina during the early stages of ischemia. Our study reveals that the SNARE-dependent exocytosis in glial cells contributes to neurotoxicity during ischemia in vivo and suggests glial exocytosis as a target for therapeutic approaches.


Subject(s)
Exocytosis/genetics , Ischemia/complications , Nerve Degeneration/etiology , Retina/pathology , Retinal Ganglion Cells/metabolism , SNARE Proteins/metabolism , Animals , Calcium-Binding Proteins/metabolism , Disease Models, Animal , Doxycycline/therapeutic use , Ependymoglial Cells/metabolism , Glial Fibrillary Acidic Protein/genetics , Glial Fibrillary Acidic Protein/metabolism , Glutamic Acid/metabolism , Intermediate Filaments/metabolism , Ischemia/pathology , Light , Mice , Mice, Transgenic , Microfilament Proteins/metabolism , Protein Kinase C-alpha/metabolism , Receptors, Purinergic P2Y1/deficiency , Receptors, Purinergic P2Y1/genetics , SNARE Proteins/genetics , Vascular Endothelial Growth Factor A/metabolism
3.
Neurochem Res ; 41(4): 677-86, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26446037

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.


Subject(s)
Inositol 1,4,5-Trisphosphate Receptors/genetics , Ischemia/pathology , Retina/pathology , Animals , Cell Count , Ependymoglial Cells/pathology , Gliosis/pathology , Mice, Knockout , Neurons/pathology
4.
Neurosci Lett ; 578: 143-7, 2014 Aug 22.
Article in English | MEDLINE | ID: mdl-24993296

ABSTRACT

It has been proposed that glutamate serves as a mediator between neurons and satellite glial cells (SGCs) in sensory ganglia and that SGCs release glutamate. Using a novel method, we studied glutamate release from SGCs from murine trigeminal ganglia. Sensory neurons with adhering SGCs were enzymatically isolated from wild type and transgenic mice in which vesicular exocytosis was suppressed in glial cells. Extracellular glutamate was detected by microfluorimetry. After loading the cells with a photolabile Ca(2+) chelator, the intracellular Ca(2+) concentration was raised in SGCs by a UV pulse, which resulted in glutamate release. The amount of released glutamate was decreased in cells with suppressed exocytosis and after pharmacological block of hemichannels. The data demonstrate that SGCs of the trigeminal ganglion release glutamate in a Ca(2+)-dependent manner.


Subject(s)
Calcium Signaling , Glutamates/metabolism , Satellite Cells, Perineuronal/metabolism , Trigeminal Ganglion/metabolism , Animals , Female , Male , Mice , Mice, Inbred C57BL , Secretory Pathway , Sensory Receptor Cells/metabolism
5.
Mol Vis ; 17: 2738-50, 2011.
Article in English | MEDLINE | ID: mdl-22065927

ABSTRACT

PURPOSE: To determine whether the human Müller cell line Moorfields/Institute of Ophthalmology-Müller 1 (MIO-M1) expresses opsins. METHODS: The gene expression of opsins was determined by reverse-transcription PCR (RT-PCR). The presence of opsin proteins was determined by western blotting and immunocytochemistry. The light sensitivity of the cells was examined with imaging experiments using the calcium-sensitive dye Fluo-4. RESULTS: MIO-M1 cells express glial (glutamine synthase [GLUL], vimentin [VIM], glial fibrillary acidic protein [GFAP], cellular retinaldehyde-binding protein [RLBP1], glial high-affinity glutamate transporter [SLCA1], aquaporin-4 [AQP4], inwardly rectifying potassium channel Kir4.1 [Kir4.1]), neuronal (Thy-1 cell surface antigen [THY1], heavy neurofilament polypeptide [NEFH], microtubule-associated protein 2 [MAP2], neurogenic differentiation 1 [NEUROD1], neuronal nuclei [NEUN]), and neural progenitor markers (Nestin [NES], paired-type homeobox transcription factor [PAX6], neurogenic locus notch homolog 1 [NOTCH1]). The cells contain mRNA for the following opsins: blue opsin (OPN1SW), rhodopsin (OPN2), panopsin (OPN3), melanopsin (OPN4), neuropsin (OPN5), and peropsin (RRH), as well as for the transducins (guanine nucleotide binding protein [GNAZ], alpha transducing activity polypeptide 1 [GNAT1], alpha transducing activity polypeptide 2 [GNAT2]). The presence of blue opsin and melanopsin was confirmed with immunocytochemistry and western blotting. The immunoreactivity and mRNA of red-green opsin were found in some but not all cultures, while the immunoreactivity for rhodopsin was absent in all cultures investigated. Repetitive stimulation with 480 nm light evoked slow and fast transient calcium responses in the majority of cells investigated, while irradiation with 600 nm light was ineffective. CONCLUSIONS: The human Müller cell line MIO-M1 expresses opsins. This suggests immortalized Müller cells could be used as a cellular source to produce human opsins for their potential application as therapeutic agents in patients with retinitis pigmentosa.


Subject(s)
Cell Line , Gene Expression/radiation effects , Opsins/biosynthesis , Retina/metabolism , Retinitis Pigmentosa/metabolism , Aniline Compounds/analysis , Blotting, Western , Calcium/metabolism , Humans , Immunohistochemistry , Light , Opsins/genetics , Opsins/pharmacology , RNA, Messenger/analysis , RNA, Messenger/biosynthesis , Retina/pathology , Retina/radiation effects , Retinitis Pigmentosa/drug therapy , Retinitis Pigmentosa/pathology , Xanthenes/analysis
SELECTION OF CITATIONS
SEARCH DETAIL
...