title: Intravitreal and subconjunctival melphalan for retinoblastoma in transgenic mice.
abstract: Purpose. To measure the chemotherapeutic effects of focal melphalan (intravitreal and subconjunctival) on tumor burden, hypoxia, and vasculature in LHBETATAG murine retinoblastoma model. Methods. LHBETATAG transgenic mice were treated with a single 1 mcg intravitreal injection of melphalan, 100 mcg subconjunctival injection, or semiweekly 10 mcg subconjunctival injections for 3 weeks. At 1 or 3 weeks, eyes were enucleated, serially sectioned, and processed with haematoxylin and eosin (H&E) for tumor burden measurements and probed with immunofluorescence to analyze tumor hypoxia and vasculature. Results. Focal melphalan significantly reduced retinal tumor size (P < 0.02) when given intravitreally or subconjunctivally. Eyes treated with a one-time intravitreal injection of 1 mcg melphalan had significantly smaller tumors at both 1 week (P = 0.017) and at 3 weeks after injection (P = 0.005). Intratumoral hypoxia showed a significant decline in hypoxia at 1 week following intravitreal injection and after maximum dosage of subconjunctival melphalan. Total vasculature was not significantly affected following intravitreal administration. Conclusion. Focal delivery of melphalan via intravitreal or subconjunctival injection has a significant effect on reducing tumor burden, hypoxia, and vasculature, in the treatment of murine retinoblastoma tumors.
authors.affiliation: Department of Ophthalmology, Tulane University, New Orleans, LA, USA.
authors.forename: Nisha V
authors.initials: NV
authors.lastname: Shah
authors.affiliation: Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, P.O. Box 016880, Miami, FL 33101, USA.
authors.forename: D G
authors.initials: DG
authors.lastname: Pham
authors.affiliation: Murray Ocular Oncology and Retina, Miami, FL, USA.
authors.forename: T G
authors.initials: TG
authors.lastname: Murray
authors.affiliation: Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, P.O. Box 016880, Miami, FL 33101, USA.
authors.forename: C
authors.initials: C
authors.lastname: Decatur
authors.affiliation: Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, P.O. Box 016880, Miami, FL 33101, USA.
authors.forename: E
authors.initials: E
authors.lastname: Hernandez
authors.affiliation: Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, P.O. Box 016880, Miami, FL 33101, USA.
authors.forename: Nikesh N
authors.initials: NN
authors.lastname: Shah
authors.affiliation: Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, P.O. Box 016880, Miami, FL 33101, USA.
authors.forename: M
authors.initials: M
authors.lastname: Cavalcante
authors.affiliation: Wills Eye Hospital, Retina Service, Philadelphia, PA, USA.
authors.forename: S K
authors.initials: SK
authors.lastname: Houston
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