Transferrin-ricin A chain toxin limits the development of experimental proliferative vitreoretinopathy

This study was designed to determine the safety and efficacy of transferrin-ricin A chain toxin (Tfr-rRA) at preventing retinal detachment in a rabbit model of proliferative vitreoretinopathy (PVR). The toxicity of intravitreal Tfr-rRA (1000-5000 ng) was determined by indirect ophthalmoscopy and electroretinography on days 1, 5, 8, 16, 26 and 48 post-injection, and by light and transmission electron microscopy conducted on eyes enucleated 48 days after drug exposure. PVR was created by injecting 25,000 homologous fibroblasts into the vitreous cavity of eyes which had previously undergone a gas compression vitrectomy. Eyes then received intravitreal Tfr-rRA (2000 ng) or vehicle. Animals were examined on days 1, 4, 7, 10, 14, 21 and 28 post-injection. Intravitreal injection of 1000 and 2000 ng Tfr-rRA did not show ophthalmoscopic or electroretinographic toxicity. Injection of 5000 ng Tfr-rRA showed mild retinal whitening, retinal arteriolar narrowing, and electroretinographic toxicity, but no morphologic damage, such as photoreceptor loss, nuclear layer vacuolation, or inflammatory cell infiltration, to the retina. Tfr-rRA (2000 ng) injected intravitreally 3 days after fibroblast injection prevented traction retinal detachment in 90% of eyes compared to 22% of sham treated eyes (P < 0.001). The data from this study suggest that transferrin-ricin A chain toxin (2000 ng) safely and effectively limits retinal detachment in experimental PVR.