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Erythropoietin schützt retinale Ganglienzellen und die Sehfunktion nach Ischämie und Sehnervkompression im Rattenmodell

Erythropoietin protects retinal ganglion cells and visual function after ocular ischemia and optic nerve compression

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Zusammenfassung

Hintergrund und Fragestellung

Das Glykoprotein Erythopoietin (EPO) schützt Neurone in zahlreichen Krankheitsmodellen und reduziert die Apopotose retinaler Ganglienzellen (RGZ) nach Durchtrennung des Sehnervs und bei Glaukom. Das Ziel war, den Effekt von EPO auf das Überleben von RGZ nach Ischämie und Sehnervkompression sowie auf die postischämische Sehfunktion im Tiermodell zu untersuchen (Neuroprotektionsmodell). Des Weiteren sollte die Verträglichkeit einer intravitrealen Injektion überprüft werden (Verträglichkeitsmodell).

Methode

EPO wurde männlichen Brown-Norway-Ratten intraokular injiziert. Eine okuläre Ischämie wurde durch Erhöhung des intraokularen Augendrucks für 55 min induziert, die kalibrierte Sehnervkompression erfolgte für 10 s nach Orbitotomie. Die RGZ wurden stereotaktisch markiert und fluoreszensmikroskopisch quantifiziert. EPO wurde in 2 Konzentrationen (2 und 20 U) im Neuroprotektionsmodell und in 3 Konzentrationen (5, 50 und 200 U) im Verträglichkeitsmodell injiziert. Die Netzhautfunktion wurde mittels Elektroretinographie (ERG) und die der gesamten Sehbahn mittels visuell evozierter Potenziale (VEP) bestimmt.

Ergebnisse

Nach Ischämie steigerte EPO (2 bzw. 20 U pro Auge, n=9–21) das Zellüberleben um 21±21% bzw. 127±31% (Mittelwert±SEM) und nach Sehnervkompression um 28±12% bzw. 58±13%. Nach Ischämie waren im ERG A-Welle und B-Welle bei 20 U EPO um 71±13% und 75±19% gesteigert. Im VEP deutete sich bei 20 U EPO ein Anstieg um 264±65% (p=0,053) an. Auf die gesunde Netzhaut hatte EPO (5, 50 und 200 U EPO, n=6-7) intravitreal appliziert keinen Effekt. Weder ERG, VEP oder die Anzahl der RGZ unterschieden sich signifikant.

Schlussfolgerung

Die Kombination aus Verträglichkeit und Schutz retinaler Neurone macht EPO zu einer viel versprechenden Substanz für die Therapie ischämischer Netzhauterkrankungen und kompressionsbedingter Optikusneuropathie.

Abstract

Background

The glycoprotein erythropoietin (EPO) has been shown to be protective in models of neuronal disease and reduced apoptosis of retinal ganglion cells (RGC) after transection of the optic nerve and in glaucoma. In this study we assessed in vivo the properties of EPO on survival of RGC after ischemia and optic nerve compression, as well as on postischemic visual function. Furthermore, the safety of intravitreal injection was assessed.

Methods

In all experiments, EPO was administered intravitreally in male Brown Norway rats. Ocular ischemia was induced by elevating the intraocular pressure for 55 min. The calibrated optic nerve compression was performed for 10 s. RGC were marked stereotactically and quantified by fluorescence microscopy. The retinal function was quantified by electroretinography (ERG) and the whole visual pathway by visual evoked potential (VEP).

Results

EPO (2 and 20 units per eye, n=9–21) increased the survival of RGC after ischemia by 21±21% and 127±31% (mean ± SEM) and after optic nerve compression by 28±12% and 58±13%. With EPO (20 units), postischemic function was increased, in ERG by 71±13% (a-wave) and 75±19% (b-wave) and in VEP by 264±65% (p=0.053). Neither the ERG parameters, nor the VEP, nor the number of RGC differed significantly after intravitreal injection of EPO (5, 50, and 200 units, n=6–7) in healthy eyes.

Conclusion

The combination of toxicological safety and protection of retinal neurons makes EPO a promising drug for ischemic retinal diseases and traumatic optic neuropathy.

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Abbreviations

EPO:

Erythropoietin

RGZ:

Retinale Ganglienzellen

ERG:

Elektroretinogaphie

VEP:

Visuell evozierte Potenziale

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Authors and Affiliations

  1. Augenklinik des Klinikums der Albert-Ludwigs-Universität Freiburg i.Br., Killianstraße 5, 79106, Freiburg i.Br., Deutschland

    T. Jehle, W. Meschede, R. Dersch, M. Bach & W.A. Lagrèze

  2. Universitäts-Augenklinik Göttingen, Göttingen, Deutschland

    N. Feltgen

Authors
  1. T. Jehle
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  2. W. Meschede
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  3. R. Dersch
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  4. N. Feltgen
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  5. M. Bach
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  6. W.A. Lagrèze
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Correspondence to T. Jehle.

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Gefördert durch die Ernst und Berta Grimmke-Stiftung.

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Jehle, T., Meschede, W., Dersch, R. et al. Erythropoietin schützt retinale Ganglienzellen und die Sehfunktion nach Ischämie und Sehnervkompression im Rattenmodell. Ophthalmologe 107, 347–353 (2010). https://doi.org/10.1007/s00347-009-2030-1

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