Wong Chee Wai, Busoy Joanna Marie Fianza, Cheung Ning, Barathi Veluchamy Amutha, Storm Gert, Wong Tina T
Singapore National Eye Centre, Singapore.
Singapore Eye Research Institute, Singapore.
Transl Vis Sci Technol. 2020 Aug 31;9(9):46. doi: 10.1167/tvst.9.9.46. eCollection 2020 Aug.
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.
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.
Three eyes (50%) and five eyes (83.3%) developed re-detachment of the retina from severe PVR in procedures A and B, respectively ( = 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, = 0.26).
This new model utilizing native RPE cells achieved a high consistency in inducing severe PVR in the minipig.
Our model closely follows pathogenic events in human PVR, making it ideal for preclinical testing of novel therapeutics for PVR.
增殖性玻璃体视网膜病变（PVR）是一种可发生于眼穿透伤和视网膜脱离后的致盲性疾病。为开发针对PVR的有效治疗方法，建立一种可重复、在解剖结构上与人类眼睛最接近且最能代表人类疾病的动物模型至关重要。我们比较了小型猪眼中两种PVR体内模型，以评估其可重复性和一致性。
6只小型猪接受了A程序诱导的PVR，6只接受了B程序。在这两种程序中，均通过玻璃体切除术、水泡性视网膜脱离、视网膜切开术和注射富血小板血浆来诱导PVR。在A程序中，从猪尸体眼睛中获取视网膜色素上皮（RPE）细胞，并在手术结束时进行注射。在B程序中，通过造成RPE脱离并刮除RPE层，将天然RPE细胞释放到玻璃体腔中。使用改良的PVR硅酮研究分类系统通过眼底镜检查对PVR严重程度进行分级。严重PVR定义为2至5期。
在A程序和B程序中，分别有3只眼（50%）和5只眼（83.3%）因严重PVR发生视网膜再次脱离（P = 0.55）。接受B程序的眼睛的PVR中位分期高于接受A程序的眼睛，尽管差异无统计学意义（2.5对1.5，P = 0.26）。
这种利用天然RPE细胞的新模型在小型猪中诱导严重PVR方面具有高度一致性。
我们的模型紧密遵循人类PVR的致病过程，使其成为PVR新型治疗方法临床前测试的理想模型。
