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G. Velez, H. Lei, A. Kazlauskas; Intravitreal STI571 Inhibition of Proliferative Vitreoretinopathy in an Experimental Rabbit Model Is Dose Dependent . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4685.
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© ARVO (1962-2015); The Authors (2016-present)
The platelet–derived growth factor (PDGF) α receptor plays an important role in the development of proliferative vitreoretinopathy (PVR) in the rabbit model. Our previous studies indicated that a high dose of intravitreal STI571, an inhibitor of PDGF α and ß receptor, effectively inhibited the development of PVR in an experimental rabbit model. Because this high dose of STI571 resulted in a number of undesirable side effects, the purpose of this study was to investigate whether low doses of STI571 can effectively inhibit PVR in the rabbit model while minimizing side effects.
PVR was induced in the R–eye of 7 Dutch pigmented rabbits by injecting 2 x 105 conjunctival fibroblasts suspended in 0.1cc of serum free DMEM, in conjunction with 0.1 cc of platelet rich plasma. This injection was preceded by a gas vitrectomy consisting of 0.1cc of 100% C3F8 three days prior. Three of the 7 rabbits (experimental group) were injected at the time of cell injection with 250 µg of STI571 suspended in 0.1cc of BSS. These rabbits were injected with an additional 250 µg dose of STI571 on Day 7. Control group rabbits were concomitantly injected with 0.1cc of BSS only. Rabbits were examined by a single investigator on Days 1, 5, 7, 14, 21, and 28 via indirect ophthalmoscopy. PVR was graded using the Fastenberg classification as follows: 0, no abnormality; 1, vitreous strands; 2, traction of the retina; 3, retinal detachment (RD) involving less than two quadrants; 4, RD including more than two quadrants; 5, total RD.
Large intravitreal cell clusters were confirmed in all injected eyes on Day 1. On Day 7, the control rabbits demonstrated development of PVR, with two each achieving stage 3 and stage 4 disease. Eyes injected with STI571 showed less severe disease with one rabbit achieving stage 1, one achieving stage 2, and one achieving stage 3 disease. On Day 28, control rabbits had achieved end–stage PVR with partial or complete RD (2 stage 3 and 2 stage 5 eyes). Of the eyes injected with STI571, one showed minimal fibrosis (stage 1), and two showed early retinal detachment (stage 3).
Intravitreal STI571 was effective in suppressing the development of PVR in a small group of rabbits and could potentially be used as a locally administered therapeutic agent for this disease. Its effect, however, is dose dependent. Further studies are needed to titrate the dose in order to achieve maximum efficacy without toxicity.
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