Department of Ophthalmology, Tianjin Medical University General Hospital, Tianjin, China.
Laboratory of Molecular Ophthalmology, Department of Pharmacology and Tianjin Key Laboratory of Inflammation Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
Invest Ophthalmol Vis Sci. 2021 Sep 2;62(12):26. doi: 10.1167/iovs.62.12.26.
To characterize vitreous microparticles (MPs) in patients with traumatic proliferative vitreoretinopathy (PVR) and investigate their role in PVR pathogenesis.
Vitreous MPs were characterized in patients with traumatic PVR, patients with rhegmatogenous retinal detachment (RRD) complicated with PVR, and control subjects by flow cytometry. The presence of M2 macrophages in epiretinal membranes was measured by immunostaining. Vitreous cytokines were quantified by ELISA assay. For in vitro studies, MPs isolated from THP-1 cell differentiated M1 and M2 macrophages, termed M1-MPs and M2-MPs, were used. The effects and mechanisms of M1-MPs and M2-MPs on RPE cell proliferation, migration, and epithelial to mesenchymal transition were analyzed.
Vitreous MPs derived from photoreceptors, microglia, and macrophages were significantly increased in patients with traumatic PVR in comparison with control and patients with RRD (PVR), whereas no significance was identified between the two control groups. M2 macrophages were present in epiretinal membranes, and their signature cytokines were markedly elevated in the vitreous of patients with traumatic PVR. Moreover, MPs from M2 macrophages were increased in the vitreous of patients with traumatic PVR. In vitro analyses showed that M2-MPs promoted the proliferation and migration of RPE cells via activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway. However, M2-MPs did not induce the expression of fibrotic proteins, including fibronectin, α-smooth muscle actin, and N-cadherin in RPE cells.
This study demonstrated increased MP shedding in the vitreous of patients with traumatic PVR; specifically, MPs derived from M2 polarized macrophages may contribute to PVR progression by stimulating RPE cell proliferation and migration.
描述创伤性增生性玻璃体视网膜病变（PVR）患者玻璃体微颗粒（MPs）的特征，并探讨其在 PVR 发病机制中的作用。
采用流式细胞术对创伤性 PVR 患者、伴有 PVR 的孔源性视网膜脱离（RRD）患者和对照组患者的玻璃体 MPs 进行特征分析。通过免疫染色测量视网膜前膜中 M2 巨噬细胞的存在。通过 ELISA 测定法定量检测玻璃体细胞因子。进行体外研究时，使用从 THP-1 细胞分化的 M1 和 M2 巨噬细胞分离的 MPs，分别称为 M1-MPs 和 M2-MPs。分析 M1-MPs 和 M2-MPs 对 RPE 细胞增殖、迁移和上皮间质转化的影响及其机制。
与对照组和 RRD（PVR）患者相比，创伤性 PVR 患者的源自光感受器、小胶质细胞和巨噬细胞的玻璃体 MPs 明显增加，而两组对照组之间无显著差异。视网膜前膜中存在 M2 巨噬细胞，其特征性细胞因子在创伤性 PVR 患者的玻璃体中明显升高。此外，创伤性 PVR 患者的玻璃体中 M2 巨噬细胞来源的 MPs 增加。体外分析表明，M2-MPs 通过激活磷脂酰肌醇 3-激酶（PI3K）/蛋白激酶 B（AKT）/雷帕霉素靶蛋白（mTOR）信号通路促进 RPE 细胞的增殖和迁移。然而，M2-MPs 不会诱导 RPE 细胞表达纤维蛋白原，包括纤维连接蛋白、α-平滑肌肌动蛋白和 N-钙粘蛋白。
本研究表明，创伤性 PVR 患者玻璃体中 MPs 的脱落增加；特别是，源自 M2 极化巨噬细胞的 MPs 可能通过刺激 RPE 细胞增殖和迁移促进 PVR 的进展。
