Abstract
Purpose: :
Alkylphosphocholines (APCs) have been shown to be an effective inhibitor of RPE cell proliferation in vitro. In this study we sought to determine the effect of APCs on Müller cell hypertrophy and proliferation induced by experimental retinal detachment in the rabbit.
Methods: :
Retinal detachments were created in adult pigmented rabbits. APCs, either bound or unbound to liposomes, was injected intravitreally on either day 1 or day 2 after detachment. BrdU was injected on day 3, 4 hours before sacrifice. Following fixation, retinas were triple labeled with anti–BrdU, Isolectin B4 (a microglia and macrophage marker) and anti–vimentin (a Müller cell Marker). The numbers of anti–BrdU labeled cells were counted per millimeter of retina from sections imaged by laser scanning confocal microscopy. Toxicity was assessed in 1 µm sections from resin embedded tissue stained with toluidine blue and viewed by light microscopy.
Results: :
A single intravitreal injection of APCs had a significant effect on reducing the number of dividing Müller cells and microglia on day three after experimental retinal detachment in the rabbit. Liposome bound drug was slightly more effective than unbound drug, and injection of the drug on day one was more effective than if given on day two. No effect was seen on Muller cell hypertrophy. In addition, no evidence of toxicity was observed in the retina at day 3 for any of the conditions.
Conclusions: :
APCs appear to be a safe, non–toxic drug that significantly reduces the number of cells that are stimulated to divide as a result of retinal detachment. This drug could be considered as an adjunct therapy at the time of retinal reattachment surgery to potentially prevent proliferative vitreoretinal diseases like PVR.
Keywords: retinal detachment • Muller cells • pharmacology