PURPOSE: Clinical evidence of retinal pigment epithelium (RPE) alterations after intra-arterial (IAC) and intravitreal chemotherapy (IViC) of retinoblastoma has been reported. We, therefore, investigated the cellular toxic effects of melphalan, topotecan and carboplatin on the RPE in a cell culture model. METHODS: The effects of melphalan, carboplatin and topotecan on ARPE19 cell morphology were examined by phase contrast microscopy. Cell proliferation was quantified by BrdU incorporation, cell viability studied via MTS assays, and cell densities were estimated by Crystal Violet staining, and apoptosis induction studied via caspase 3/7-activity assays after a 24-hr incubation period. Staurosporine, media without fetal bovine serum, diluents of melphalan, carboplatin and topotecan were applied as positive and negative controls, respectively. RESULTS: We observed a concentration-dependent increase in the number and size of gaps in the ARPE19 cell layer with each drug. There was a significant decrease in proliferative activity and cell viability of RPE cells as well as an increase in apoptosis after 24 hrs culture in media supplemented with melphalan and topotecan. Carboplatin had comparable effects on cell proliferation and cell viability; however, no significant apoptotic impacts were observed. The three cytostatic drugs had insignificant effects on cell density measurements. CONCLUSIONS: Morphological monitoring and toxicity assays indicate a direct toxic effect of melphalan and the other two cytostatic drugs on ARPE19 cells. Thus, a direct toxic effect of melphalan in vivo after IAC or IViC on the RPE seems probable and may explain the clinical and angiographic RPE alterations observed in some retinoblastoma patients.
PURPOSE: Clinical evidence of retinal pigment epithelium (RPE) alterations after intra-arterial (IAC) and intravitreal chemotherapy (IViC) of retinoblastoma has been reported. We, therefore, investigated the cellular toxic effects of melphalan, topotecan and carboplatin on the RPE in a cell culture model. METHODS: The effects of melphalan, carboplatin and topotecan on ARPE19 cell morphology were examined by phase contrast microscopy. Cell proliferation was quantified by BrdU incorporation, cell viability studied via MTS assays, and cell densities were estimated by Crystal Violet staining, and apoptosis induction studied via caspase 3/7-activity assays after a 24-hr incubation period. Staurosporine, media without fetal bovine serum, diluents of melphalan, carboplatin and topotecan were applied as positive and negative controls, respectively. RESULTS: We observed a concentration-dependent increase in the number and size of gaps in the ARPE19 cell layer with each drug. There was a significant decrease in proliferative activity and cell viability of RPE cells as well as an increase in apoptosis after 24 hrs culture in media supplemented with melphalan and topotecan. Carboplatin had comparable effects on cell proliferation and cell viability; however, no significant apoptotic impacts were observed. The three cytostatic drugs had insignificant effects on cell density measurements. CONCLUSIONS: Morphological monitoring and toxicity assays indicate a direct toxic effect of melphalan and the other two cytostatic drugs on ARPE19 cells. Thus, a direct toxic effect of melphalan in vivo after IAC or IViC on the RPE seems probable and may explain the clinical and angiographic RPE alterations observed in some retinoblastomapatients.
Authors: Anthony B Daniels; Michael T Froehler; Amy H Nunnally; Janene M Pierce; Ivan Bozic; Cameron A Stone; Pranav R Santapuram; Yuankai K Tao; Kelli L Boyd; Lauren E Himmel; Sheau-Chiann Chen; Liping Du; Debra L Friedman; Ann Richmond Journal: Invest Ophthalmol Vis Sci Date: 2019-03-01 Impact factor: 4.799
Authors: Paula Schaiquevich; Jasmine H Francis; María Belén Cancela; Angel Montero Carcaboso; Guillermo L Chantada; David H Abramson Journal: Front Oncol Date: 2022-04-01 Impact factor: 5.738
Authors: Lisa McAnena; Zishan Naeem; Catriona Duncan; Fergus Robertson; Mandeep S Sagoo; M Ashwin Reddy Journal: Am J Ophthalmol Case Rep Date: 2020-01-30
Authors: Yacoub A Yousef; Mays Al Jboor; Mona Mohammad; Mustafa Mehyar; Mario D Toro; Rashed Nazzal; Qusai H Alzureikat; Magdalena Rejdak; Mutasem Elfalah; Iyad Sultan; Robert Rejdak; Maysa Al-Hussaini; Ibrahim Al-Nawaiseh Journal: Front Pharmacol Date: 2021-07-12 Impact factor: 5.810