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Erythropoietin protects from axotomy-induced degeneration of retinal ganglion cells by activating ERK-1/-2.
FASEB J. 2005 Feb; 19(2):249-51.FJ

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.

Authors+Show Affiliations

Department of Neurology, University Hospital Zurich, Switzerland. uelkan.kilic@usz.chNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15556972

Citation

Kilic, Ulkan, et al. "Erythropoietin Protects From Axotomy-induced Degeneration of Retinal Ganglion Cells By Activating ERK-1/-2." FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology, vol. 19, no. 2, 2005, pp. 249-51.
Kilic U, Kilic E, Soliz J, et al. Erythropoietin protects from axotomy-induced degeneration of retinal ganglion cells by activating ERK-1/-2. FASEB J. 2005;19(2):249-51.
Kilic, U., Kilic, E., Soliz, J., Bassetti, C. I., Gassmann, M., & Hermann, D. M. (2005). Erythropoietin protects from axotomy-induced degeneration of retinal ganglion cells by activating ERK-1/-2. FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology, 19(2), 249-51.
Kilic U, et al. Erythropoietin Protects From Axotomy-induced Degeneration of Retinal Ganglion Cells By Activating ERK-1/-2. FASEB J. 2005;19(2):249-51. PubMed PMID: 15556972.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Erythropoietin protects from axotomy-induced degeneration of retinal ganglion cells by activating ERK-1/-2. AU - Kilic,Ulkan, AU - Kilic,Ertugrul, AU - Soliz,Jorge, AU - Bassetti,Claudio I, AU - Gassmann,Max, AU - Hermann,Dirk M, Y1 - 2004/11/19/ PY - 2004/11/24/pubmed PY - 2005/9/22/medline PY - 2004/11/24/entrez SP - 249 EP - 51 JF - FASEB journal : official publication of the Federation of American Societies for Experimental Biology JO - FASEB J VL - 19 IS - 2 N2 - 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. SN - 1530-6860 UR - https://www.unboundmedicine.com/medline/citation/15556972/Erythropoietin_protects_from_axotomy_induced_degeneration_of_retinal_ganglion_cells_by_activating_ERK_1/_2_ L2 - https://doi.org/10.1096/fj.04-2493fje DB - PRIME DP - Unbound Medicine ER -