Heffer Alison, Wang Victor, Sridhar Jayanth, Feldon Steven E, Libby Richard T, Woeller Collynn F, Kuriyan Ajay E
Flaum Eye Institute, University of Rochester, Rochester, NY, USA.
Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA.
Transl Vis Sci Technol. 2020 Jun 5;9(7):9. doi: 10.1167/tvst.9.7.9. eCollection 2020 Jun.
Develop a reproducible proliferative vitreoretinopathy (PVR) mouse model that mimics human PVR pathology.
Mice received intravitreal injections of SF gas, followed by retinal pigment epithelial cells 1 week later. PVR progression was monitored using fundus photography and optical coherence tomography imaging, and histologic analysis of the retina as an endpoint. We developed a PVR grading scheme tailored for this model.
We report that mice that received gas before retinal pigment epithelial injection developed more severe PVR. In the 1 × 10 retinal pigment epithelial cell group, after 1 week, 0 of 11 mice in the no gas group developed grade 4 or greater PVR compared with 5 of 13 mice in the SF gas group ( = 0.02); after 4 weeks, 3 of 11 mice in the no gas group developed grade 5 or greater PVR compared with 11 of 14 mice in the SF gas group ( = 0.01). We were able to visualize contractile membranes both on the retinal surface as well as within the vitreous of PVR eyes, and demonstrated through immunohistochemical staining that these membranes expressed fibrotic markers alpha smooth muscle actin, vimentin, and fibronectin, as well as other markers known to be found in human PVR membranes.
This mouse PVR model is reproducible and mimics aspects of PVR pathology reported in the rabbit PVR model and human PVR. The major advantage is the ability to study PVR development in different genetic backgrounds to further elucidate aspects of PVR pathogenesis. Additionally, large-scale experiments for testing pharmacologic agents to treat and prevent PVR progression is more feasible compared with other animal models.
This model will provide a platform for screening potential drug therapies to treat and prevent PVR, as well as elucidate different molecular pathways involved in PVR pathogenesis.
建立一种可重复的增殖性玻璃体视网膜病变（PVR）小鼠模型，该模型可模拟人类PVR病理过程。
小鼠接受玻璃体内注射SF气体，1周后注射视网膜色素上皮细胞。使用眼底摄影和光学相干断层扫描成像监测PVR进展，并将视网膜组织学分析作为终点。我们为该模型制定了一个PVR分级方案。
我们报告称，在注射视网膜色素上皮细胞之前接受气体注射的小鼠发生了更严重的PVR。在1×10视网膜色素上皮细胞组中，1周后，未接受气体注射组的11只小鼠中0只发生4级或更高级别的PVR，而SF气体组的13只小鼠中有5只发生（P = 0.02）；4周后，未接受气体注射组的11只小鼠中有3只发生5级或更高级别的PVR，而SF气体组的14只小鼠中有11只发生（P = 0.01）。我们能够在PVR眼睛的视网膜表面以及玻璃体内可视化收缩膜，并通过免疫组织化学染色证明这些膜表达纤维化标志物α平滑肌肌动蛋白、波形蛋白和纤连蛋白，以及已知在人类PVR膜中发现的其他标志物。
该小鼠PVR模型具有可重复性，可模拟兔PVR模型和人类PVR中报道的PVR病理特征。主要优点是能够在不同遗传背景下研究PVR的发展，以进一步阐明PVR发病机制的各个方面。此外，与其他动物模型相比，用于测试治疗和预防PVR进展的药物的大规模实验更可行。
该模型将为筛选治疗和预防PVR的潜在药物疗法提供一个平台，同时阐明PVR发病机制中涉及的不同分子途径。
