Abstract
Purpose :
Proliferative vitreoretinopathy (PVR) is the most common cause of failure of surgically repaired rhegmatogenous retinal detachment (RRD). Chemically-induced and cell-injection PVR models have been developed, but there is an unmet need for translational models in which to evaluate potential therapies specific to RRD-PVR. The objective of this study was to characterize the histologic and immunohistochemical features of a rabbit model of RRD-PVR at acute and chronic time points.
Methods :
Posterior segments of enucleated globes from male and female Dutch Belted rabbits were harvested and frozen or formalin-fixed at 6 hours and 2, 14, and 35 days following unilateral induction of RRD-PVR by vitrectomy and retinotomy followed by retinal cryotherapy and intravitreal platelet-rich plasma injection (n = 8 rabbits/time point); contralateral globes served as controls. Routine H&E and Masson’s trichrome staining and immunolabeling for glial fibrillary acidic protein (GFAP), vascular endothelial growth factor receptor 2 (VEGFR2), CD68, retinal pigment epithelium 65 kDa protein (RPE65), and laminin were performed on all sections, and labeling intensity was scored (0: absent, 1: weak, 2: moderate, 3: strong).
Results :
Acute histopathologic changes included intravitreal and intraretinal hemorrhage, heterophilic vitritis, chorioretinitis, and retinal necrosis, while chronic lesions included retinal atrophy, gliosis, subretinal fibrotic membranes, and epiretinal fibrovascular proliferation in the region of the medullary streak. Trichrome-positive fibrillar collagen was present in the subretinal fibrocellular and epiretinal fibrovascular membranes at days 14 and 35 along with increased expression of laminin. Moderate to strong GFAP and VEGFR2 labeling was detected in chronic RRD-PVR lesions. RPE65 expression was absent in dedifferentiated subretinal RPE cells in chronic RRD-PVR lesions.
Conclusions :
Histologic features of this rabbit model may effectively simulate important late features of human RRD-PVR including epiretinal and subretinal membrane formation. These findings suggest that developing high-fidelity in vivo models for RRD-PVR is essential to enable further research on targeted treatment interventions.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.