Header

UZH-Logo

Maintenance Infos

Erythropoietin protects from axotomy-induced degeneration of retinal ganglion cells by activating ERK-1/-2 - Zurich Open Repository and Archive


Kilic, Ulkan; Kilic, Ertugrul; Soliz, Jorge; Bassetti, Claudio I; Gassmann, Max; Hermann, Dirk M (2005). Erythropoietin protects from axotomy-induced degeneration of retinal ganglion cells by activating ERK-1/-2. FASEB Journal, 19(2):249-251.

Abstract

Apart from its hematopoietic function, erythropoietin (Epo) exerts neuroprotective activity upon reduced oxygenation or ischemia of brain, retina, and spinal cord. To examine whether Epo has an impact on the retrograde degeneration of retinal ganglion cells (RGCs) following optic nerve transection in vivo, we made use of our transgenic mouse line tg21 that constitutively expresses human Epo preferentially in neuronal cells without inducing polycythemia. We show that the tg21 retina expresses human Epo and that RGCs in this mouse line carry the Epo receptor. Upon axotomy, the RGCs of Epo transgenic tg21 mice were protected against degeneration, as compared with wild-type control animals. Western blot analysis revealed decreased phosphorylation levels of STAT-5 and reduced expression of Bcl-XL in RGCs of axotomized tg21 animals, suggesting that the corresponding pathways are not crucial for Epo's neuroprotective activity. Increased phosphorylation levels of ERK-1/-2 and Akt, as well as decreased caspase-3 activity, however, were observed in injured tg21 retinae. Injection of selective inhibitors of ERK-1/-2 (PD98059) or Akt (Wortmannin) pathways into the vitreous space revealed that transgenic Epo protected the RGCs by a pathway involving ERK-1/-2 but not Akt. In view that axotomy-induced degeneration of RGC occurs slowly, and considering the earlier data on the safety and efficacy of Epo in human stroke patients, we predict the clinical implementation of recombinant human Epo not only in patients with acute ischemic stroke, but also with more delayed degenerative neurological diseases.

Abstract

Apart from its hematopoietic function, erythropoietin (Epo) exerts neuroprotective activity upon reduced oxygenation or ischemia of brain, retina, and spinal cord. To examine whether Epo has an impact on the retrograde degeneration of retinal ganglion cells (RGCs) following optic nerve transection in vivo, we made use of our transgenic mouse line tg21 that constitutively expresses human Epo preferentially in neuronal cells without inducing polycythemia. We show that the tg21 retina expresses human Epo and that RGCs in this mouse line carry the Epo receptor. Upon axotomy, the RGCs of Epo transgenic tg21 mice were protected against degeneration, as compared with wild-type control animals. Western blot analysis revealed decreased phosphorylation levels of STAT-5 and reduced expression of Bcl-XL in RGCs of axotomized tg21 animals, suggesting that the corresponding pathways are not crucial for Epo's neuroprotective activity. Increased phosphorylation levels of ERK-1/-2 and Akt, as well as decreased caspase-3 activity, however, were observed in injured tg21 retinae. Injection of selective inhibitors of ERK-1/-2 (PD98059) or Akt (Wortmannin) pathways into the vitreous space revealed that transgenic Epo protected the RGCs by a pathway involving ERK-1/-2 but not Akt. In view that axotomy-induced degeneration of RGC occurs slowly, and considering the earlier data on the safety and efficacy of Epo in human stroke patients, we predict the clinical implementation of recombinant human Epo not only in patients with acute ischemic stroke, but also with more delayed degenerative neurological diseases.

Citations

1 citation in Web of Science®
100 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

0 downloads since deposited on 15 Apr 2015
0 downloads since 12 months

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Neurology
05 Vetsuisse Faculty > Institute of Veterinary Physiology
Dewey Decimal Classification:570 Life sciences; biology
Date:February 2005
Deposited On:15 Apr 2015 13:14
Last Modified:05 Apr 2016 19:13
Publisher:Federation of American Society of Experimental Biology
ISSN:0892-6638
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1096/fj.04-2493fje
PubMed ID:15556972

Download

Preview Icon on Download
Filetype: PDF - Registered users only
Size: 875kB
View at publisher

TrendTerms

TrendTerms displays relevant terms of the abstract of this publication and related documents on a map. The terms and their relations were extracted from ZORA using word statistics. Their timelines are taken from ZORA as well. The bubble size of a term is proportional to the number of documents where the term occurs. Red, orange, yellow and green colors are used for terms that occur in the current document; red indicates high interlinkedness of a term with other terms, orange, yellow and green decreasing interlinkedness. Blue is used for terms that have a relation with the terms in this document, but occur in other documents.
You can navigate and zoom the map. Mouse-hovering a term displays its timeline, clicking it yields the associated documents.

Author Collaborations