Abstract:AIM: To determine the effect of the tyrphostin AG1295 and AG1296, a selective blocker of platelet-derived growth factor (PDGF) β and α RTK, on proliferative vitreoretinopathy (PVR) development. METHODS: Rabbit conjunctival fibroblasts (RCF) cells were cultured. The effects of AG1295, AG1296, PDGF-AA and PDGF-BB on RCF proliferation were evaluated by MTT assay. Homologous rabbit conjunctival fibroblasts were injected intravitreally to make animal PVR model, followed by injection of 100μmol/L of AG1295 or AG1296 respectively. The presence of tractional retinal detachment (TRD) was assessed to evaluate the effect of AG1295 and AG1296 in vivo. Electroretinography and histologic studies were performed after intravitreal injection of AG1295 into untreated eyes to evaluate toxicity. · RESULTS: Both AG1295 and AG1296 (10μmol/L) significantly inhibited rabbit conjunctival fibroblast cell growth stimulated by PDGF-AA or -BB in vitro . Development of TRD was significantly reduced (P <0.05) with 100μmol/L of AG1295 or AG1296 in vivo , but the effect of AG1295 only present until day 14. Inhibitive effect of AG1296 was longer than that of AG1295. No significant histological or retinal functional damage was found in both drug-treated groups. CONCLUSION: PDGF α and β receptor specific inhibitor AG1296 and AG1295 attenuate PVR without significant side effects in rabbits, and AG1296 is better than AG1295. The much longer and stronger therapeutic effect from PDGF α receptor inhibitor indicates that PDGF α receptor is more important in the development of PVR, and inhibition of this pathway can be a useful treatment alternative to prevent PVR.
