Department of Ophthalmology, University of Washington, Seattle, Washington, United States.
Department of Biological Structure, University of Washington, Seattle, Washington, United States.
Invest Ophthalmol Vis Sci. 2018 May 1;59(6):2504-2511. doi: 10.1167/iovs.18-24192.
To compare lymphocyte populations present within inflamed eyes in two rat models of autoimmune uveitis.
Experimental autoimmune uveitis (EAU) and primed mycobacterial uveitis (PMU) were initiated in Lewis rats. Aqueous and vitreous were collected at peak inflammation (PMU at day 2, EAU at day 14). The number of cells in the aqueous and vitreous was determined and compared for each eye and between the two models. Intraocular CD-19+ B cells, CD3+ T cells, and CD4+ or CD8+ T-cell subpopulations were identified by flow cytometry and compared between EAU and PMU.
The median number of cells/mL collected from PMU aqueous (7.98 × 107 cells/mL), was not significantly different from the number of cells collected from EAU aqueous (1.61 × 107 cells/mL, P = 0.94). EAU aqueous contains a significantly larger mononuclear population (median 61%, interquartile range [IQR] 44%-67%) than PMU (median 9%, IQR 8%-10% [P < 0.0001]). Within the mononuclear population, EAU and PMU aqueous demonstrate similar proportions of CD3+, CD4+ T cells. However, EAU has a larger CD3+, CD8+, T-cell population than PMU, and this population also demonstrates co-expression of CD45R. B cells comprise a significantly larger median percentage of cells in EAU aqueous (median 18%, IQR 15%-20%) compared to PMU (median 13%, IQR 9%-15%, P = 0.006).
Flow cytometry analysis of intraocular lymphocytes from EAU and PMU identifies similarities and differences between the T-cell and B-cell populations present at peak inflammation. Complementary animal models that have well-defined mechanistic differences will improve our ability to test potential new therapies and bring meaningful advances into clinical practice for patients with uveitis.
比较两种自身免疫性葡萄膜炎大鼠模型中炎症眼内的淋巴细胞群。
在 Lewis 大鼠中引发实验性自身免疫性葡萄膜炎（EAU）和原代分枝杆菌性葡萄膜炎（PMU）。在炎症高峰期（PMU 第 2 天，EAU 第 14 天）收集房水和玻璃体液。比较每只眼和两种模型之间的房水和玻璃体液中的细胞数量。通过流式细胞术鉴定眼内 CD-19+B 细胞、CD3+T 细胞以及 CD4+或 CD8+T 细胞亚群，并比较 EAU 和 PMU 之间的差异。
从 PMU 房水中收集的细胞数/mL（中位数 7.98×107 个细胞/mL）与从 EAU 房水中收集的细胞数/mL（中位数 1.61×107 个细胞/mL，P=0.94）无显著差异。EAU 房水中的单核细胞群体（中位数 61%，四分位距[IQR]44%-67%）显著大于 PMU（中位数 9%，IQR 8%-10%[P<0.0001]）。在单核细胞群体中，EAU 和 PMU 房水均显示出相似比例的 CD3+、CD4+T 细胞。然而，EAU 中的 CD3+、CD8+T 细胞群体比 PMU 更大，并且该群体也表现出 CD45R 的共表达。与 PMU（中位数 13%，IQR 9%-15%，P=0.006）相比，EAU 房水中的 B 细胞占细胞中位数的比例明显更大（中位数 18%，IQR 15%-20%）。
通过对 EAU 和 PMU 眼内淋巴细胞的流式细胞术分析，确定了炎症高峰期存在的 T 细胞和 B 细胞群体之间的相似性和差异。具有明确机制差异的互补动物模型将提高我们测试潜在新疗法的能力，并为葡萄膜炎患者带来有意义的临床实践进展。
