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Investigating short-term toxicity of melphalan in a model of an isolated and superfused bovine retina

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Abstract

Background

Melphalan, as a treatment for retinoblastoma, has been applied intra-arterially by catheterisation of the ophthalmic artery or intravitreally, aiming to reduce systemic side effects of intravenous drug therapy. This study evaluates retinal toxicity of different melphalan concentrations measured by electroretinogram (ERG) in an isolated and perfused retinal whole mount culture.

Methods

For functional testing, bovine retinas were prepared and perfused with an oxygen-saturated standard solution and the ERG was recorded until stable b-wave or a-wave amplitudes were reached. Thereafter, retinae were exposed to 80, 160 and 320 μg/ml of melphalan for 30 min. After exposure, a washout was performed thrice for 5 min each and the ERG amplitude recovery was monitored for 60 min. To investigate the effects on photoreceptor function, 1-mM asparate was added to suppress the b-wave and obtain isolated a-waves.

Results

While no toxic effects for a concentration of 80 μg/ml were observed, both b- and a-waves were significantly reduced after application of 160 (b-wave 43.8 %, p = 0.03; a-wave 28.2 %, p = 0.04) and 320 μg/ml (b-wave 20.0 %, p = 0.04; a-wave 35.8 %, p = 0.02). For 320 μg/ml, this reduction remained significant at the end of the washout (b-wave 40.0 % p = 0.02; a-wave 26.4 %, p = 0.02).

Conclusions

Epiretinal or intraretinal concentrations of 80-μg/ml melphalan do not cause toxic effects in this in vitro model. Concentrations higher than 160 μg/ml should be avoided.

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Acknowledgments

This work was supported by the Ernst-und-Berta-Grimmke-Foundation. We would like to thank Jolene C. Hayes for her language review and wish her all the best for the exciting times to come. Thanks to Regina Ebenhoch for her support. Also, thanks to Till Bechtold, Oli Borst, Sascha Hoffman, David Schilling and Andreas Schmidt for fruitful discussions.

Conflict of interest

All authors certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.

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Authors and Affiliations

  1. Centre for Ophthalmology, University Eye Hospital Tübingen, Schleichstr. 12, D-72076, Tübingen, Germany

    Kai Januschowski, Carlo Krupp, Sebastian Mueller, Kathleen Hofmann, Sven Schnichels, Ulrike Hagemann, Martin S. Spitzer & Karl-Ulrich Bartz-Schmidt

  2. Eye hospital, Knappschaftklinikum, Sulzbach, Saar, Germany

    Kai Januschowski

  3. University Eye Hospital, University of Oldenburg, Oldenburg, Germany

    Sabine Aisenbrey

Authors
  1. Kai Januschowski
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  2. Carlo Krupp
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  3. Sebastian Mueller
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  4. Kathleen Hofmann
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  6. Ulrike Hagemann
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  7. Martin S. Spitzer
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  8. Karl-Ulrich Bartz-Schmidt
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  9. Sabine Aisenbrey
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Correspondence to Kai Januschowski.

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Januschowski, K., Krupp, C., Mueller, S. et al. Investigating short-term toxicity of melphalan in a model of an isolated and superfused bovine retina. Graefes Arch Clin Exp Ophthalmol 254, 91–96 (2016). https://doi.org/10.1007/s00417-015-3149-1

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  • DOI: https://doi.org/10.1007/s00417-015-3149-1

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