Kai Januschowski1,2, Carlo Krupp3, Sebastian Mueller3, Kathleen Hofmann3, Sven Schnichels3, Ulrike Hagemann3, Martin S Spitzer3, Karl-Ulrich Bartz-Schmidt3, Sabine Aisenbrey4. 1. Centre for Ophthalmology, University Eye Hospital Tübingen, Schleichstr. 12, D-72076, Tübingen, Germany. Kai.januschowski@med.uni-tuebingen.de. 2. Eye hospital, Knappschaftklinikum, Sulzbach, Saar, Germany. Kai.januschowski@med.uni-tuebingen.de. 3. Centre for Ophthalmology, University Eye Hospital Tübingen, Schleichstr. 12, D-72076, Tübingen, Germany. 4. University Eye Hospital, University of Oldenburg, Oldenburg, Germany.
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.
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.
Authors: Kai Januschowski; Ahmad Zhour; Albert Lee; Ramin Maddani; Sebastien Mueller; Martin S Spitzer; Sven Schnichels; Maximilian Schultheiss; Deshka Doycheva; Karl-Ulrich Bartz-Schmidt; Peter Szurman Journal: Altern Lab Anim Date: 2012-03 Impact factor: 1.303
Authors: Kai Januschowski; Sebastian Mueller; Martin S Spitzer; Charlotte Schramm; Deshka Doycheva; Karl-Ulrich Bartz-Schmidt; Peter Szurman Journal: Graefes Arch Clin Exp Ophthalmol Date: 2012-03-28 Impact factor: 3.117
Authors: Jasmine H Francis; Paula Schaiquevich; Emiliano Buitrago; María José Del Sole; Gustavo Zapata; J Oscar Croxatto; Brian P Marr; Scott E Brodie; Alejandro Berra; Guillermo L Chantada; David H Abramson Journal: Ophthalmology Date: 2014-05-10 Impact factor: 12.079
Authors: Dan S Gombos; John Hungerford; David H Abramson; Judith Kingston; Guillermo Chantada; Ira J Dunkel; Celia B G Antoneli; Mark Greenwald; Barret G Haik; Carlos A Leal; Aurora Medina-Sanson; Amy C Schefler; Gavivann Veerakul; Regina Wieland; Norbert Bornfeld; Mathew W Wilson; Christopher Bing On Yu Journal: Ophthalmology Date: 2007-07 Impact factor: 12.079