The anemia of the newborn induces erythropoietin expression in the developing mouse retina

N. Scheerer, N. Dünker, S. Imagawa, M. Yamamoto, N. Suzuki, J. Fandrey

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

The hematopoietic hormone erythropoietin (Epo), regularly produced by the kidneys and the liver, is also expressed in neuronal tissue, where it has been found to mediate paracrine neuroprotective effects. In most studies exploring the rescue effects of Epo, apoptosis was exogenously induced by different cell death stimuli. Herein, we set out to study the expression and function of Epo in physiologically occurring apoptosis in a model of retinal development. We made use of an organotypic retinal wholemount culture system that resembles the physiological in vivo situation with cell connections still retained. Epo mRNA expression in the retina, liver, and kidney showed a significant increase during early development, coinciding with the anemia of the newborn. In the retina of Epo-green fluorescent protein transgenic mice, Epo-expressing cells were identified and found to be distributed in the retinal ganglion cell layer. Treatment of retinal wholemount cultures with recombinant Epo resulted in a significant decrease of apoptotic ganglion cells as well as photoreceptor cells throughout retinal development. Moreover, transforming growth factor-β-induced apoptosis was completely antagonized by Epo when both factors were simultaneously applied. Investigations on the signaling pathway revealed a decrease in Bax mRNA levels in Epo-treated retinal cells. We conclude that Epo exerts wide and prolonged neuroprotective activity in physiologically occurring apoptosis and thus contributes to proper retinal development.

Original languageEnglish
Pages (from-to)R111-R118
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume299
Issue number1
DOIs
Publication statusPublished - 2010 Jul 1
Externally publishedYes

Keywords

  • Apoptosis
  • Erythropoietin receptor
  • Neuroprotection
  • Retinal ganglion cells

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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