Effect of Erythropoietin Axotomy-Induced Apoptosis in Rat Retinal Ganglion Cells

Weishaupt, Jochen H.; Rohde, Gundula; Pölking, Esther; Sirén, Anna‐Leena; Ehrenreich, Hannelore; Bähr, Mathias

doi:10.1167/iovs.03-1039

Cited by 173 publications

(157 citation statements)

References 62 publications

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“…10 U/mL) did not show stronger protective effects. Several studies have confirmed this particular dose-response behavior of EPO in vivo [17,18] , which might have relevance to the design of the upcoming clinical trials. As the recent human stroke study has demonstrated, EPO has beneficial effect on neurons in the context of cerebral ischemia [19] .…”

Section: Discussionsupporting

confidence: 54%

Protective effect of erythropoietin against 1-methyl-4-phenylpyridinium-induced neurodegenaration in PC12 cells

Shang

Sun

et al. 2007

Neurosci. Bull.

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Objective The neuroprotective effect of erythropoietin (EPO) against 1-methyl-4-phenylpyridinium (MPP + )-induced oxidative stress in cultured PC12 cells, as well as the underlying mechanism, were investigated. Methods PC12 cells impaired by MPP + were used as the cell model of Parkinson's disease. Methyl thiazolyl tetrazolium (MTT) was used to assay the viability of the PC12 cells exposed to gradient concentrations of EPO, and the terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay was used to analyze the apoptosis ratio of PC12 cells. The expression of Bcl-2 and Bax in PC12 cells were examined by Western blot, and the reactive oxygen species (ROS), the mitochondrial transmembrane potential and the activity of caspase-3 in each group were detected by spectrofluorometer. Results Treatment of PC12 cells with MPP + caused the loss of cell viability, which may be associated with the elevation in apoptotic rate, the formation of ROS and the disruption of mitochondrial transmembrane potential. It was also shown that MPP + significantly induced the upregulation of Bax/Bcl-2 ratio and the activation of caspase-3. In contrast, EPO significantly reversed these responses and had the maximum protective effect at 1 U/mL. Conclusion The inhibitive effect of EPO on the MPP + -induced cytotoxicity may be ascribed to its anti-oxidative property and anti-apoptotic activity, and EPO may provide a useful therapeutic strategy for treatment of neurodegenerative diseases such as Parkinson's disease.

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Section: Discussionsupporting

confidence: 54%

Protective effect of erythropoietin against 1-methyl-4-phenylpyridinium-induced neurodegenaration in PC12 cells

Shang

Sun

et al. 2007

Neurosci. Bull.

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“…Antiapoptotic effects of Epo on immunopurified RGCs have been demonstrated recently in vitro, indicating that Epo acts directly on these neurons. 48 Additionally, in this study intravitreal applications of Epo were shown to prevent RGC death after surgical transection of the ON. As the intravitreal approach causes structural damage to the rat eye after repetitive applications, we used systemic applications of Epo in our present study.…”

Section: Discussionmentioning

confidence: 71%

Neuroprotective effects and intracellular signaling pathways of erythropoietin in a rat model of multiple sclerosis

Sättler¹,

Merkler

Maier³

et al. 2004

Cell Death Differ

165

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In multiple sclerosis (MS), long-term disability is primarily caused by axonal and neuronal damage. We demonstrated in a previous study that neuronal apoptosis occurs early during experimental autoimmune encephalomyelitis, a common animal model of MS. In the present study, we show that, in rats suffering from myelin oligodendrocyte glycoprotein (MOG)-induced optic neuritis, systemic application of erythropoietin (Epo) significantly increased survival and function of retinal ganglion cells (RGCs), the neurons that form the axons of the optic nerve. We identified three independent intracellular signaling pathways involved in Epo-induced neuroprotection in vivo: Protein levels of phospho-Akt, phospho-MAPK 1 and 2, and Bcl-2 were increased under Epo application. Using a combined treatment of Epo together with a selective inhibitor of phosphatidylinositol 3-kinase (PI3-K) prevented upregulation of phospho-Akt and consecutive RGC rescue. We conclude that in MOG-EAE the PI3-K/Akt pathway has an important influence on RGC survival under systemic treatment with Epo.

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“…Several studies showed that PI 3-kinase/Akt pathway plays a major role in mediating the survival response of retinal ganglion cells after axotomy to a variety of growth factors. [12][13][14] In addition, apoptosis of retinal neurons induced by serum deprivation was reduced by insulin via activating the PI 3-kinase/Akt pathway. 15 Furthermore, retinal PI 3-kinase/Akt signalling pathway was activated by optic nerve clamping and had a neuroprotective effect on injured retinal ganglion cells.…”

Section: Discussionmentioning

confidence: 99%

“…[11][12][13][14][15][16] Several studies showed that Cox-2 functions as a survival factor by protecting cells from apoptosis. [17][18][19][20][21] Overexpression of Mcl-1, a member of the Bcl-2 family, 22 delays apoptosis by a broad array of agents.…”

mentioning

confidence: 99%

Expression of antiapoptotic and proapoptotic molecules in diabetic retinas

El‐Asrar

Dralands

Missotten

et al. 2006

Eye

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Effect of Erythropoietin Axotomy-Induced Apoptosis in Rat Retinal Ganglion Cells

Cited by 173 publications

References 62 publications

Protective effect of erythropoietin against 1-methyl-4-phenylpyridinium-induced neurodegenaration in PC12 cells

Protective effect of erythropoietin against 1-methyl-4-phenylpyridinium-induced neurodegenaration in PC12 cells

Neuroprotective effects and intracellular signaling pathways of erythropoietin in a rat model of multiple sclerosis

Expression of antiapoptotic and proapoptotic molecules in diabetic retinas

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