Intravitreal Tissue Plasminogen Activator Injection for the Treatment of Proliferative Vitreoretinopathy in a Rabbit Model

Abstract

Introduction: The purpose of this study was to evaluate the effect of intravitreal injection of tissue plasminogen activator (tPA) on proliferative vitreoretinopathy (PVR). Methods: PVR was induced in a rabbit model by intraocular injection of dispase (0.05 U/0.1 mL). Progression of PVR was followed by indirect ophthalmic examination. Following 6 weeks, 5 animals received intravitreal injection of 25 µg/0.1 mL tPA and four were injected with balanced salt solution (BSS). Animals were euthanized at 48 h following tPA/BSS injection, and eyes were enucleated for histological evaluation and staining with α-smooth muscle actin (αSMA) and Sirius Red. Results: Following tPA injection, one eye had a reduction in PVR from grade 2 to 1 and three eyes remained stable. Following BSS, PVR grade was unchanged in three eyes. In one eye in each group, the severity of PVR could not be assessed due to limited view. Staining with αSMA showed reduced presence of fibroblasts in eyes injected with tPA compared with those injected with BSS. Collagen type I and III, demonstrated by Sirius Red staining, was reduced in the tPA group in comparison with controls. Conclusion: Our results suggest that intravitreally injected tPA may show an inhibitory effect on PVR progression. Further exploration in clinical trials is desired.