A novel mouse model of proliferative vitreoretinopathy induced by intravitreal injection of gas and RPE cells.

Abstract

Purpose : To develop a reproducible mouse model of proliferative vitreoretinopathy (PVR) that mimics human PVR pathology.

Methods : Mice received an intravitreal injection of SF₆ gas to promote posterior vitreous detachment, followed by an injection of RPE cells one week later. We monitored the progression of PVR using fundus and optical coherence tomography (OCT) ocular imaging, as well as histological analysis of the retina as an endpoint. We also developed a PVR grading scheme appropriate for our model.

Results : After 1 week, 0 of 11 (0%) mice in the no gas/1x10⁴ RPE cell group developed Grade 4 or worse PVR compared to 5 of 13 (38%) mice in the SF₆ gas/1x10⁴ RPE mice group (p = 0.02). After 4 weeks, 3 of 11 (27%) mice in the no gas/1x10⁴ RPE cell group developed Grade 5 or worse PVR compared to 11 of 14 (79%) mice in the SF₆ gas/1x10⁴ RPE cell group (p = 0.01). After 1 week, 5 of 12 (42%) mice in the no gas/5x10⁴ RPE cell group developed Grade 4 or worse PVR compared to 8 of 13 (62%) mice in the SF₆ gas/5x10⁴ RPE cell group (p = 0.32). After 4 weeks, 7 of 13 (54%) mice in the no gas/5x10⁴ RPE cell group developed Grade 5 or worse PVR compared to 11 of 12 (92%) mice in the SF₆ gas/5x10⁴ RPE mice group (p = 0.03). None of the control eyes injected with gas and PBS developed any characteristics of PVR (all Grade 0). Contractile membranes were visualized both on the retinal surface as well as within the vitreous and immunohistochemical staining demonstrated that these membranes expressed fibrotic markers alpha smooth muscle actin (αSMA), Collagen I (Col1A1) and fibronectin (FN1), which markers of epithelial-mesenchymal transition, known to be elevated found in human PVR membranes.

Conclusions : Our mouse reproducible PVR model mimics many aspects of PVR pathology seen in a commonly used rabbit PVR model and human PVR. These results demonstrate that an intravitreal SF₆ injection prior to RPE injection resulted in more severe PVR development. The major advantage is that a mouse model of PVR provides is the ability to study PVR development with different genetic backgrounds to further elucidate aspects of PVR pathogenesis. Additionally, the mouse model is more amenable to larger scale experiments for testing of different pharmacological agents to treat and prevent PVR progression, due to cost and space requirements, compared to rabbits.

This is a 2020 ARVO Annual Meeting abstract.