Topoisomerase II inhibitors for proliferative vitreoretinopathy

郭锡恭1 PEI-CHANG WU,1 PO-MIN YANG,1 YI-HAO CHEN,1 YI-CHAN WU,1 and DAN-NING HU2
1Department of Ophthalmology, Chang-Gung Memorial Hospital-Kaohsiung Medical Center, Kaohsiung, Taiwan；2Tissue Culture Center, New York Eye and Ear Infirmary, New York Medical College, New York, USA

    Purpose: The aim of this study was to compare the effect of some commercially available topoisomerase II inhibitors on the proliferation of retinal pigment epithelium (RPE) cells in vitro and test the toxicity and efficacy against experimental proliferative vitreoretinopathy (PVR).
    Methods: Study medications included etoposide, doxorubicin, and daunorubicin. Rabbit RPE cells were seeded without (control) or with the drugs at various medicine concentrations (100, 30, 10, 1.0, 0.1, 0.01ug/ml). MTT assay was used to determine cell survival and proliferation rate at 48hours and 96hours. Four rabbits were used to study toxicity of etoposide To evaluate retinal toxicity, bilateral simultaneous electroretinograms (ERGs) were obtained. Five rabbits were used to further study the efficacy of etoposide against experimental PVR.
    Results: The slope of dose-response curve was slowly declined for etoposide, but very sharp for doxorubicin and daunorubicin in MTT assay. Etoposide was selected for further toxicity and efficacy tests. There was no significant change in b-wave amplitudes in etoposide (0.02 mg, 10μg/ml)-injected eyes after 2 weeks, but significant reduction in etoposide (0.2 mg, 100μg/ml)-injected eyes. Ten days after gas compression vitrectomy with 0.4 ml SF6, the right eyes of rabbits were injected with 1×105 cells of RPE and etoposide (0.02 mg/ 0.1 cc PBS) and the left eyes were injected with 1×105 cells of RPE and PBS 0.1cc. In the first 2 weeks, etoposide-injected eyes had statistically significant lower grading of PVR than the control eyes.
    Conclusions: These results demonstrated etoposide would be an adjunctive for the prevention of PVR. Further pharmacokinetic study of intravitreal injection of etoposide is necessary for repeated intravitreal administrations.

声明:本站独家报道，转载须标明来源“中华眼科在线”