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G. Velez, A. Kazlauskas, M. Young; SU9518 Inhibits Proliferative Vitreoretinopathy (PVR) in a Rabbit Model. Invest. Ophthalmol. Vis. Sci. 2010;51(13):6086.
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Platelet derived growth factor receptor alpha (PDGFRα) has been shown to play an important role in the development of PVR in both human specimens and animal models of the disease. In a rabbit model using fibroblasts, disabling the PDGFRα has been shown to inhibit development of fibrous proliferation and contraction. SU9518 is a tyrosine kinase inhibitor which targets PDGFRα. We examine whether intravitreal injection of SU9518 in our rabbit model can effectively inhibit the development of PVR.
24 rabbits underwent gas vitrectomy to their right eye with 0.1 ml of C3F8, followed one week later by intravitreal injection of 2x105 rabbit conjunctival fibroblasts (RCFs) in 0.1 ml of DMEM and 0.1ml of platelet rich plasma (PRP). 17 of these rabbits were injected with 300 µg of SU9518 in 0.1ml of BSS at the time of gas injection. Eyes were examined by indirect ophthalmoscopy at days 2, 4, 7 and weekly thereafter for a total of 4 weeks after cell injection. Extent of PVR was graded each time using the Fastenberg classification: stage 0- no PVR, stage1- fibrous bands in vitreous, stage 2- fibrous bands with retinal traction, stage 3- retinal detachment (RD) less than two quadrants, stage 4- RD more than two quadrants, stage 5- total RD. Stages 0 to 2 are considered mild PVR, stages 3 to 5 severe.
At day 7, 3/7 control rabbits had developed stage 3 PVR, 4/7 had developed stage 4. In the experimental group treated with SU9518, 2/17 rabbits had no PVR (stage 0), 6/17 stage 1, 7/17 stage 2 and only 2/17 stage 3. By day 28, all eyes in the control group had developed severe PVR (1/7 stage 4, 6/7 stage 5). In the experimental group, no eyes developed severe PVR (4/17 stage 0, 6/17 stage 1, and 7/17 stage 2). None of the experimental eyes showed signs of retinal toxicity.
SU9518 is an effective inhibitor of PVR in our rabbit model, and could potentially be used in humans for the treatment of PVR and other proliferative diseases involving fibrosis and gliosis. Further animal studies need to be performed to examine retinal toxicity as well as sustained delivery mechanisms.
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