Departments of Ophthalmology, Tokyo Medical University, Tokyo, Japan.
Invest Ophthalmol Vis Sci. 2012 Aug 9;53(9):5395-402. doi: 10.1167/iovs.11-8719.
Various immune mediators are hypothesized to have important roles in the pathogenesis of vitreoretinal B-cell lymphoma, although the exact mechanisms remain unclear. We determined the immune mediator profile in the vitreous of eyes with vitreoretinal B-cell lymphoma.
We studied 28 eyes (23 patients) with vitreoretinal B-cell lymphoma, and 27 eyes (27 patients) undergoing vitrectomy for macular hole and epiretinal membrane served as controls. Undiluted vitreous samples were collected, and cytometric bead array and ELISA were used to determine the vitreous concentrations of 38 immune mediators, including 14 interleukins (IL); interferon (IFN)-γ; oncostatin M (OSM); IFN-γ-inducible protein (IP)-10; monocyte chemoattractant protein (MCP)-1; macrophage inflammatory protein (MIP)-1α; MIP-1β, regulated on activation, normal T-cell expressed and secreted (RANTES); monokine induced by IFN-γ (Mig); stromal cell-derived factor (SDF)-1α; B-cell-attracting chemokine (BCA)-1; basic fibroblast growth factor (bFGF); Fas ligand; granzyme A; and granzyme B.
Vitreous levels of BCA-1, bFGF, Fas ligand, granzyme A, granzyme B, IFN-γ, IL-6, IL-8, IL-10, IP-10, MCP-1, Mig, MIP-1α, MIP-1β, OSM, RANTES, and SDF-1α were significantly higher in vitreoretinal B-cell lymphoma patients than in controls. A moderate-to-strong positive correlation was observed between granzyme A and BCA-1, IFN-γ, or MIP-1β; between IFN-γ and Mig or SDF-1α; between IL-6 and IL-8, IL-10, IP-10, or MCP-1; between IL-8 and MCP-1, Mig, or MIP-1β; between IL-10 and MCP-1 or MIP-1α; between Mig and IP-10 or Mig; and between MIP-1α and MIP-1β.
Our study suggested that elevated vitreous levels of various immune mediators inducing growth, migration, and apoptosis of B-cell lymphoma are involved possibly in the pathophysiology of vitreoretinal B-cell lymphoma.
尽管确切的发病机制仍不清楚,但各种免疫介质被认为在眼内B 细胞淋巴瘤的发病机制中具有重要作用。我们确定了眼内 B 细胞淋巴瘤患者玻璃体中的免疫介质谱。
我们研究了 28 只眼(23 例患者)的眼内 B 细胞淋巴瘤,并以 27 只眼(27 例患者)因黄斑裂孔和视网膜前膜而行玻璃体切除术作为对照。收集未经稀释的玻璃体样本,并使用流式细胞术微珠阵列和 ELISA 来确定 38 种免疫介质(包括 14 种白细胞介素(IL)、干扰素(IFN)-γ、肿瘤坏死因子(OSM)、IFN-γ诱导蛋白(IP)-10、单核细胞趋化蛋白(MCP)-1、巨噬细胞炎性蛋白(MIP)-1α、MIP-1β、调节激活正常 T 细胞表达和分泌(RANTES)、γ干扰素诱导的单核细胞趋化蛋白(Mig)、基质细胞衍生因子(SDF)-1α、B 细胞趋化因子(BCA)-1、碱性成纤维细胞生长因子(bFGF)、Fas 配体、颗粒酶 A 和颗粒酶 B)在玻璃体中的浓度。
眼内 B 细胞淋巴瘤患者的玻璃体 BCA-1、bFGF、Fas 配体、颗粒酶 A、颗粒酶 B、IFN-γ、IL-6、IL-8、IL-10、IP-10、MCP-1、Mig、MIP-1α、MIP-1β、OSM、RANTES 和 SDF-1α 的水平明显高于对照组。在颗粒酶 A 与 BCA-1、IFN-γ 或 MIP-1β;IFN-γ 与 Mig 或 SDF-1α;IL-6 与 IL-8、IL-10、IP-10 或 MCP-1;IL-8 与 MCP-1、Mig 或 MIP-1β;IL-10 与 MCP-1 或 MIP-1α;Mig 与 IP-10 或 Mig;MIP-1α 与 MIP-1β 之间观察到中度至强的正相关。
我们的研究表明,各种免疫介质在玻璃体中的水平升高,这些免疫介质可诱导 B 细胞淋巴瘤的生长、迁移和凋亡,可能参与了眼内 B 细胞淋巴瘤的病理生理学过程。