Depletion of optineurin in RGC-5 cells derived from retinal neurons causes apoptosis and reduces the secretion of neurotrophins

Sippl, Christiane; Bosserhoff, Anja‐Katrin; Fischer, Dietmar; Tamm, Ernst R.

doi:10.1016/j.exer.2011.08.011

Cited by 40 publications

(44 citation statements)

References 67 publications

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“…In the course of these studies, apoptosis of retinal ganglion cells was observed in addition to functional deficits detected by ERG. Moreover, in the RGC-5 cell line, which is derived from retinal progenitors (Van Bergen et al, 2009;Sippl et al, 2011), TGF-␤1 decreased apoptosis (Walshe et al, 2011), similarly to the action of TGF-␤2 on retinal ganglion cells in dissociated retinal cultures in our study.…”

Section: Tgfb1supporting

confidence: 62%

“…Finally, we treated cultures from the RGC-5 cell line that displays mouse retinal progenitor cell characteristics with recombinant TGF-␤2. RGC-5 cells were first treated with staurosporine to induce a differentiated phenotype (Sippl et al, 2011). When TGF-␤2 was added at a concentration of 3 ng/ml, we observed a significant increase ( p ϭ 0.012) in the levels of NGF mRNA, which was blocked completely ( p ϭ 0.006) upon inhibiting TGF-␤ signaling with SIS3 (Fig.…”

Section: The Expression Of Ngf In the Retina Of Mouse Pups Is Regulatmentioning

confidence: 87%

“…In addition, Cell Death Detection ELISA (Roche Diagnostics) was used, which determines histone-associated DNA fragments (mononucleosomes and oligonucleosomes) in the cytoplasmatic fraction of cell lysates. Paraffin sections were investigated following the manufacturer's instructions and previously reported protocols (Seitz et al, 2010;Sippl et al, 2011). For quantitative analysis, the number of TUNEL-positive nuclei in midsagittal sections throughout the entire retina was counted and normalized to the area of the retina that was measured using Axiovision software 3.0 (Carl Zeiss).…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

TGF- Signaling Protects Retinal Neurons from Programmed Cell Death during the Development of the Mammalian Eye

Braunger

Pielmeier

Demmer

et al. 2013

Journal of Neuroscience

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We investigated the influence of transforming growth factor-␤ (TGF-␤) signaling on developmental programmed cell death in the mouse retina by direct and specific molecular targeting of TGF-␤ type II receptor (T␤RII) and Smad7 in retinal progenitor cells. Mice were generated carrying a conditional deletion of the T␤RII in cells that originate from the inner layer of the optic cup. The animals showed a significant decrease of phosphorylated Smad3 in both the central and peripheral retina, which indicates the diminished activity of TGF-␤ signaling. T␤RII deficiency significantly increased the apoptotic death of retinal neurons during embryonic and postnatal development without affecting their proliferation. In contrast, treatment with TGF-␤2 inhibited cell death of retinal ganglion cells in dissociated retinal cell cultures, an effect that was blocked by inhibiting the phosphorylation of Smad3. The increase in apoptosis during development resulted in a significant reduction in the number of neurons in adult T␤RII-deficient mice. The effect was most pronounced in the inner retina neurons and resulted in functional deficits as determined by electroretinography. In contrast, a conditional deletion of TGF-␤-inhibiting Smad7 in retinal neurons significantly enhanced Smad3 phosphorylation and significantly decreased apoptosis of retinal neurons in embryos and pups. Moreover, the number of retinal ganglion cells was significantly higher in Smad7-deficient mice compared with control littermates. T␤RII-deficient pups showed a lower level of nerve growth factor (NGF) in its mRNA; however, higher levels were observed in Smad7-deficient pups, which strongly suggests that the protective effects of TGF-␤ signaling on developmental cell death are mediated through NGF.

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Section: Tgfb1supporting

confidence: 62%

Section: The Expression Of Ngf In the Retina Of Mouse Pups Is Regulatmentioning

confidence: 87%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

TGF- Signaling Protects Retinal Neurons from Programmed Cell Death during the Development of the Mammalian Eye

Braunger

Pielmeier

Demmer

et al. 2013

Journal of Neuroscience

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show abstract

“…26,27,29,32 Indeed, in RGC5 cells derived from retinal neurons that are dependent on both autocrine and paracrine signaling of neurotrophic factors for their growth, Optn deficiency led to decreased secretion of neurotrophic factors and increased apoptotic death. 33 The release of secreted proteins to the extracellular environment requires the formation of a fusion pore (porosome). The fusion pore is an aqueous channel that is formed upon the fusion of the vesicle membrane with the plasma membrane.…”

mentioning

confidence: 99%

Toward an integrative view of Optineurin functions

et al. 2012

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“…This cell line does not recapitulate all electrophysiological features of normal RGCs, but it is sensitive to excitotoxity and neurotrophin withdrawal (14). Therefore, RGC-5 cells, which are neuronal precursor-like cells, provide a valuable tool to study molecular/biochemical mechanisms underlying the pathogenesis of retinal neurodegenerative diseases (15,16).…”

mentioning

confidence: 99%

Neuroprotective Effects of Methyl 3,4-dihydroxybenzoate Against H2O2-Induced Apoptosis in RGC-5 Cells

Zhou

Zhang

et al. 2014

J Pharmacol Sci

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Depletion of optineurin in RGC-5 cells derived from retinal neurons causes apoptosis and reduces the secretion of neurotrophins

Cited by 40 publications

References 67 publications

TGF- Signaling Protects Retinal Neurons from Programmed Cell Death during the Development of the Mammalian Eye

TGF- Signaling Protects Retinal Neurons from Programmed Cell Death during the Development of the Mammalian Eye

Toward an integrative view of Optineurin functions

Neuroprotective Effects of Methyl 3,4-dihydroxybenzoate Against H2O2-Induced Apoptosis in RGC-5 Cells

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