RETINAL TOXICITY OF THE ANTIMETABOLITE 5-FLUOROURIDINE 5'-MONOPHOSPHATE ADMINISTERED INTRAVITREALLY USING MULTIVESICULAR LIPOSOMES

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Abstract
Liposome-encapsulated 5-fluorouridine-5'-monophosphate (FUMP) has been shown to inhibit proliferative vitreoretinopathy in a rabbit model. Liposome encapsulation extends the intravitreal half-life of this antiproliferative drug by a factor of 28 times. The current study investigated the retinal toxicity of intravitreal injections of 10, 50, and 100 micrograms FUMP as free drug or within liposomes in rabbits. Evaluation included ophthalmoscopic examination, electroretinography, and histologic analysis by light and electron microscopy. No electroretinographic evidence for toxicity of FUMP was found. Light and electron microscopy showed only mild transient vacuolization in the outer segment layer, without inflammation. Empty liposomes incurred no toxic effects on the retina. Our results suggest that liposome-encapsulated FUMP may be non-toxic to the retina at doses that inhibit proliferative retinopathy.

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