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

TY - JOUR

T1 - Investigating short-term toxicity of melphalan in a model of an isolated and superfused bovine retina

AU - Januschowski, Kai

AU - Krupp, Carlo

AU - Mueller, Sebastian

AU - Hofmann, Kathleen

AU - Schnichels, Sven

AU - Hagemann, Ulrike

AU - Spitzer, Martin S

AU - Bartz-Schmidt, Karl-Ulrich

AU - Aisenbrey, Sabine

PY - 2016/1

Y1 - 2016/1

N2 - 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.

AB - 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.

KW - Animals

KW - Antineoplastic Agents, Alkylating

KW - Aspartic Acid

KW - Cattle

KW - Dark Adaptation

KW - Electroretinography

KW - Melphalan

KW - Organ Culture Techniques

KW - Photic Stimulation

KW - Photoreceptor Cells, Vertebrate

KW - Retina

KW - Retinal Ganglion Cells

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1007/s00417-015-3149-1

DO - 10.1007/s00417-015-3149-1

M3 - SCORING: Journal article

C2 - 26335534

VL - 254

SP - 91

EP - 96

JO - GRAEF ARCH CLIN EXP

JF - GRAEF ARCH CLIN EXP

SN - 0721-832X

IS - 1

ER -