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

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 diffe...

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Bibliographic Details
Published in:American journal of physiology. Regulatory, integrative and comparative physiology integrative and comparative physiology, 2010-07, Vol.299 (1), p.R111-R118
Main Authors: Scheerer, N, Dünker, N, Imagawa, S, Yamamoto, M, Suzuki, N, Fandrey, J
Format: Article
Language:English
Subjects:
Anemia
Anemia - genetics
Anemia - metabolism
Animals
Animals, Newborn
Apoptosis
Apoptosis - drug effects
Apoptosis - genetics
Apoptosis - physiology
bcl-2-Associated X Protein - genetics
bcl-2-Associated X Protein - metabolism
Erythropoietin - genetics
Erythropoietin - metabolism
Erythropoietin - pharmacology
Hormones
Humans
Mice
Mice, Inbred C57BL
Mice, Transgenic
Neurons - metabolism
Photoreceptor Cells
Recombinant Proteins
Retina
Retina - metabolism
Retinal Ganglion Cells - metabolism
Ribonucleic acid
RNA
RNA, Messenger - genetics
RNA, Messenger - metabolism
Rodents
Signal Transduction - genetics
Specific Pathogen-Free Organisms
Transforming Growth Factor beta - pharmacology
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Summary: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-beta-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.
ISSN:0363-6119
1522-1490
1522-1490
DOI:10.1152/ajpregu.00108.2010