Purchase this article with an account.
F. Suarez, M.E. Jockovich, E. Hernandez, J.M. Parel, T.G. Murray; Taxol in the Treatment of Retinal Tumors of LH BETATAG Murine Transgenic Model of Retinoblastoma . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2801.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
The purpose of this study is to investigate tumor control efficacy of Paclitaxel in the treatment of retinal tumors harbored by LHBETATAG–a murine transgenic model of retinoblastoma.
The study protocol was approved by the University of Miami, School of Medicine Animal Care and Use Review Board, Miami, Fla. All experiments in this study were conducted in accordance with the Association for Research in Vision and Ophthalmology guidelines for the use of animals in ophthalmologic and vision research. Paclitaxel was dissolved in 100% DMSO to final concentrations of 0.5 mg/20µl, or 0.25 mg/20µl. LHBETATAG positive mice of 10 weeks of age received two 20µl subconjunctival injections delivered weekly to right eyes only; left eyes served as untreated controls. Control mice received two subconjunctival injections of DMSO. Eyes were enucleated at 16 weeks of age, stained with Haematoxylin & Eosin and histopathologically examined for residual tumor volume.
Histological assessment of tumor volume suggests a dose dependent tumor response to the combined treatment. A statistically significant (p<0.05) reduction in tumor burden is detected with all doses of Paclitaxel relative to DMSO–treated, fellow eyes and untreated controls. Ocular toxicity was observed in all mice following injection and the severity of toxic effects was dose dependent. For example, eyes injected with DMSO alone showed only slight toxicity after injection, while eyes injected with the 0.5 mg/20µl dose showed the most severe toxicity. Signs of toxicity included iris neovascularization, inflammation of the conjunctiva and cataract formation, but at 16 weeks of age most of the toxicity had noticeably subsided in the lower dose and in DMSO alone treated eyes. After histological assessment the lower dose had effectively controlled tumor burden and was associated with only minimal toxicity.
Subconjunctival delivery of Paclitaxel effectively inhibits intraocular tumor burden in the LHBETATAG model of retinoblastoma. Although ocular toxicity is evident at the higher dose, tumor control with minimal associated toxicity can be achieved following two weekly subconjunctival injections of at 0.25 mg of Paclitaxel. This treatment modality may represent a novel strategy for the treatment of pediatric retinoblastoma.
This PDF is available to Subscribers Only