Endogenous or Exogenous Retinal Pigment Epithelial Cells: A Comparison of Two Experimental Animal Models of Proliferative Vitreoretinopathy

Abstract

Purpose: Proliferative vitreoretinopathy (PVR) is a blinding condition that can occur following ocular penetrating injury and retinal detachment. To develop effective therapeutics for PVR, it is imperative to establish an animal model that is reproducible, closest in anatomy to the human eye, and most representative of the human disease. We compared two in vivo models of PVR in minipig eyes to assess reproducibility and consistency. Methods: Six minipigs underwent PVR induction with procedure A and six underwent procedure B. In both procedures, PVR was induced with vitrectomy, bleb retinal detachment, retinotomy, and injection of platelet-rich plasma. In procedure A, retinal pigment epithelial (RPE) cells were harvested from cadaveric pig eyes and injected at the end of surgery. In procedure B, native RPE cells were released into the vitreous cavity by creating a RPE detachment and scraping the RPE layer. PVR severity was graded on fundoscopic examination with a modified Silicone Study Classification System for PVR. Severe PVR was defined as stages 2 to 5. Results: Three eyes (50%) and five eyes (83.3%) developed re-detachment of the retina from severe PVR in procedures A and B, respectively (P = 0.55). Median PVR stage was higher in eyes that underwent procedure B compared to eyes that underwent procedure A, although the difference was not statistically significant (2.5 vs. 1.5, P = 0.26). Conclusions: This new model utilizing native RPE cells achieved a high consistency in inducing severe PVR in the minipig. Translational Relevance: Our model closely follows pathogenic events in human PVR, making it ideal for preclinical testing of novel therapeutics for PVR.