Pre-treatment of adult rats with high doses of erythropoietin induces caspase-9 but prevents light-induced retinal injury

Ranchon-Cole, Isabelle; Bonhomme, Brigitte; Doly, M.

doi:10.1016/j.exer.2007.08.013

Cited by 14 publications

(7 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We detected photoreceptor rescue with a single injection of 10U of EPO thirteen days prior to analysis despite rapid clearance of the protein – only half the amount of EPO detected at time zero could be detected one hour later. Levels of EPO equivalent to previously published neuroprotective doses of 24–39mU/mg in the retina (Grimm et al, 2004; Kilic et al, 2005; Ranchon Cole et al, 2007) were reached about 11 hours post-injection. It is possible that a continuous dose of up to 1257mU/ml EPO in the eye was above the neuroprotective dose range of EPO.…”

Section: Discussionsupporting

confidence: 56%

Neuroprotection of photoreceptors by direct delivery of erythropoietin to the retina of the retinal degeneration slow mouse

Rex

Wong

Kodali

et al. 2009

Experimental Eye Research

View full text Add to dashboard Cite

The primary objectives of this study were to determine if erythropoietin (EPO) is neuroprotective to the photoreceptors in the retinal degeneration slow (rds) mouse in the absence of an increase in hematocrit and to determine if deglycosylated EPO (DEPO) is less neuroprotective. We performed subretinal injections of 10U EPO, DEPO or hyperglycosylated EPO (HEPO) in postnatal day 7 rds mice. Whole eye EPO levels were quantified by ELISA at specified time points post-injection. TUNEL analysis, hematocrit, and immunohistochemistry were performed at postnatal day 20. Half of the amount of EPO measured immediately after injection was detected less than one hour later. Twenty four hours later, EPO levels were 1000 times lower than the amount originally detected. Uninjected rds mice contained 36±2 TUNEL-positive cells/mm retina and PBS injected mice contained 17±3 TUNEL-positive cells/mm retina. EPO, DEPO, and HEPO treated rds retinas contained 5±2, 9±2, and 3±1 TUNEL-positive cells/mm retina, respectively. The hematocrit was 43% in control and 41% in treated rds mice Previous studies have shown neuroprotection of the retina by treatment with as little as 24–39mU EPO/mg total protein in the eye. In this study, we detected 40mU/mg EPO in the eye 11 hours after injecti on of 10U EPO. Treatment with all forms of EPO tested was neuroprotective to the photoreceptors without a concomitant increase in hematocrit.

show abstract

Section: Discussionsupporting

confidence: 56%

Neuroprotection of photoreceptors by direct delivery of erythropoietin to the retina of the retinal degeneration slow mouse

Rex

Wong

Kodali

et al. 2009

Experimental Eye Research

View full text Add to dashboard Cite

show abstract

“…This is a compilation of data from this and other studies [7, 8, 42]. No protection was achieved with intraocular EPO levels of 0.03, 0.06, or 32mU (this study, [8]).…”

Section: Fig (1)mentioning

confidence: 70%

“…It would be interesting to know how much EPO they detected in the eye at various time-points after injection of the nanoparticles. Ranchon-Cole et al showed that IP injection of 5000U/kg EPO in the rat resulted in approximately 15mU EPO/mg total protein in the eye at 8-16 hours after injection [42]. Considering the average protein content of a rat retina is 1mg, they detected approximately 15mU EPO in the eye and this level was neuroprotective.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Identification of a Therapeutic Dose of Continuously Delivered Erythropoietin in the Eye Using An Inducible Promoter System

Hines-Beard

Desai

Haag

et al. 2013

CGT

View full text Add to dashboard Cite

Erythropoietin (EPO) can protect the retina from acute damage, but long-term systemic treatment induces polycythemia. Intraocular gene delivery of EPO is not protective despite producing high levels of EPO likely due to its bell-shaped dose curve. The goal of this study was to identify a therapeutic dose of continuously produced EPO in the eye. We packaged a mutated form of EPO (EPOR76E) that has equivalent neuroprotective activity as wild-type EPO and attenuated erythropoietic activity into a recombinant adeno-associated viral vector under the control of the tetracycline inducible promoter. This vector was injected into the subretinal space of homozygous postnatal 5-7 day retinal degeneration slow mice, that express the tetracycline transactivators from a retinal pigment epithelium specific promoter. At weaning, mice received a single intraperitoneal injection of doxycycline and were then maintained on water with or without doxycycline until postnatal day 60. Intraocular EPO levels and outer nuclear layer thickness were quantified and correlated. Control eyes contained 6.1 ± 0.1 (SEM) mU/ml EPO. The eyes of mice that received an intraperitoneal injection of doxycycline contained 11.8 ± 2.0 (SEM) mU/ml EPO-R76E. Treatment with doxycycline water induced production of 35.9 ± 2.4 (SEM) mU/ml EPO-R76E in the eye. The outer nuclear layer was approximately 8μm thicker in eyes of mice that received doxycycline water as compared to the control groups. Our data indicates that drug delivery systems should be optimized to deliver at least 36mU/ml EPO into the eye since this dose was effective for the treatment of a progressive retinal degeneration.

show abstract

“…Erythropoietin and its receptor, EpoR, have been shown to be expressed in rodent and human brains, in cultured neurons, astrocytes, oligodendrocytes, microglia, and endothelial cells, which have led to studies investigating the additional biological roles of EPO [10]. Erythropoietin and EpoR in the CNS and the upregulation of EPO by hypoxia/ischemia in vitro and in vivo suggest that this cytokine is an important mediator of the response of the brain to injury [11]. The suggested neuroprotective effects of EPO include antagonism against the deleterious action of glutamate, increase in the expression of antioxidant enzymes, decrease in free-radical production, augmentation in the release of neurotransmitters, increased pro-angiogenic activity and induction of neuroglobin (an intracerebral O 2 transporter) [12].…”

Section: Introductionmentioning

confidence: 99%

Neuroprotective effects of erythropoietin against oxidant injury following brain irradiation: an experimental study

Uğurluer

Çebi

Mert

et al. 2016

aoms

View full text Add to dashboard Cite

IntroductionRadiation therapy (RT) is a major treatment modality, and the central nervous system is a dose-limiting organ in clinical RT. This experimental study aims to present the evaluation of the neuroprotective effects of erythropoietin (EPO) against oxidant injury following brain irradiation in rats.Material and methodsForty Wistar rats were randomly assigned to four groups (n = 10 each). In group 1 the rats received no EPO and underwent sham RT. The rats in groups 2 and 3 received EPO. In group 2 rats underwent sham RT, while in group 3 rats received RT. The rats in group 4 received no EPO and underwent RT. Rats were irradiated using a Cobalt-60 teletherapy machine using a single fraction of 20 Gy covering the whole brain. Cervical dislocation euthanasia was performed. The nitrite and malondialdehyde (MDA) levels and the superoxide dismutase (SOD) and glutathione peroxidase (GSHPX) activities were evaluated in dissected brain tissues.ResultsThe nitrite and MDA levels were higher in the RT group (2.10 ±0.62 ppm, 26.02 ±2.16 nmol/ml; p < 0.05) and lower in the EPO + RT group (1.45 ±0.12 ppm, 25.49 ±1.90 nmol/ml; p < 0.05). The SOD and GSHPX activity was higher in the EPO + RT group (2.62 ±0.49 U/mg, 1.75 ±0.25 U/mg, p < 0.05).ConclusionsThis study supports the probable neuroprotective effects of EPO against oxidant injury following brain irradiation in a rat model, presumably through decreasing free radical production and increasing expression of antioxidant enzymes.

show abstract

Pre-treatment of adult rats with high doses of erythropoietin induces caspase-9 but prevents light-induced retinal injury

Cited by 14 publications

References 34 publications

Neuroprotection of photoreceptors by direct delivery of erythropoietin to the retina of the retinal degeneration slow mouse

Neuroprotection of photoreceptors by direct delivery of erythropoietin to the retina of the retinal degeneration slow mouse

Identification of a Therapeutic Dose of Continuously Delivered Erythropoietin in the Eye Using An Inducible Promoter System

Neuroprotective effects of erythropoietin against oxidant injury following brain irradiation: an experimental study

Contact Info

Product

Resources

About