PMID: 9430558Jan 16, 1998Paper

Intravitreal daunomycin induces multidrug resistance in proliferative vitreoretinopathy

Investigative Ophthalmology & Visual Science
P EsserM Weller

Abstract

Adjuvant intravitreal daunomycin is frequently used for the management of proliferative vitreoretinopathy (PVR). In this study the authors examined whether daunomycin could induce multidrug resistance (MDR), mediated by the mdr-1 gene product P-glycoprotein, in the cells responsible for reproliferation in vivo and in human retinal pigment epithelial (RPE) cells in vitro. Expression of P-glycoprotein was examined by immunohistochemistry in surgically removed epiretinal membranes. The cellular source of P-glycoprotein was examined by colabeling for cytokeratin, glial fibrillary acidic protein, and the macrophage marker EBM-11. P-glycoprotein expression by cultured RPE cells was assessed by reverse transcription-polymerase chain reaction and immunoblot analysis. Daunomycin toxicity was quantified by crystal violet assay. P-glycoprotein expression was detected in 10 of 10 patients pre-exposed to intravitreal daunomycin. In contrast, epiretinal membranes from only 2 of 13 patients never exposed to daunomycin showed faint P-glycoprotein expression. P-glycoprotein expression was strong within 8 months after daunomycin treatment and faded thereafter. Colocalization studies demonstrated predominant expression of P-glycoprotein by RPE ce...Continue Reading

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