Pepple Kathryn L, Rotkis Lauren, Van Grol Jennifer, Wilson Leslie, Sandt Angela, Lam Deborah L, Carlson Eric, Van Gelder Russell N
Department of Ophthalmology, University of Washington, Seattle, Washington, United States.
Alcon Research Laboratories, Fort Worth, Texas, United States.
Invest Ophthalmol Vis Sci. 2015 Dec;56(13):8438-48. doi: 10.1167/iovs.15-17523.
The purpose of this study was to compare the histologic features and cytokine profiles of experimental autoimmune uveitis (EAU) and a primed mycobacterial uveitis (PMU) model in rats.
In Lewis rats, EAU was induced by immunization with interphotoreceptor binding protein peptide, and PMU was induced by immunization with a killed mycobacterial extract followed by intravitreal injection of the same extract. Clinical course, histology, and the cytokine profiles of the aqueous and vitreous were compared using multiplex bead fluorescence immunoassays.
Primed mycobacterial uveitis generates inflammation 2 days after intravitreal injection and resolves spontaneously 14 days later. CD68+ lymphocytes are the predominant infiltrating cells and are found in the anterior chamber, surrounding the ciliary body and in the vitreous. In contrast to EAU, no choroidal infiltration or retinal destruction is noted. At the day of peak inflammation, C-X-C motif ligand 10 (CXCL10), IL-1β, IL-18, and leptin were induced in the aqueous of both models. Interleukin-6 was induced 2-fold in the aqueous of PMU but not EAU. Cytokines elevated in the aqueous of EAU exclusively include regulated on activation, normal T cell expressed and secreted (RANTES), lipopolysaccharide-induced CXC chemokine (LIX), growth-related oncogene/keratinocyte chemokine (GRO/KC), VEGF, monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α), and IL-17A. In the vitreous, CXCL10, GRO/KC, RANTES, and MIP-1α were elevated in both models. Interleukin-17A and IL-18 were elevated exclusively in EAU.
Primed mycobacterial uveitis generates an acute anterior and intermediate uveitis without retinal involvement. Primed mycobacterial uveitis has a distinct proinflammatory cytokine profile compared with EAU, suggesting PMU is a good complementary model for study of immune-mediated uveitis. CXCL10, a proinflammatory cytokine, was increased in the aqueous and vitreous of both models and may be a viable therapeutic target.
本研究旨在比较大鼠实验性自身免疫性葡萄膜炎（EAU）和致敏分枝杆菌性葡萄膜炎（PMU）模型的组织学特征和细胞因子谱。
在Lewis大鼠中，通过光感受器间结合蛋白肽免疫诱导EAU，通过用灭活的分枝杆菌提取物免疫，随后玻璃体内注射相同提取物诱导PMU。使用多重微珠荧光免疫测定法比较临床病程、组织学以及房水和玻璃体的细胞因子谱。
致敏分枝杆菌性葡萄膜炎在玻璃体内注射后2天引发炎症，并在14天后自发消退。CD68+淋巴细胞是主要的浸润细胞，见于前房、睫状体周围和玻璃体。与EAU不同，未观察到脉络膜浸润或视网膜破坏。在炎症高峰期，两种模型的房水中均诱导产生C-X-C基序配体10（CXCL10）、IL-1β、IL-18和瘦素。PMU房水中白细胞介素-6诱导增加2倍，而EAU中未增加。EAU房水中特异性升高的细胞因子包括活化调节正常T细胞表达和分泌因子（RANTES）、脂多糖诱导的CXC趋化因子（LIX）、生长相关癌基因/角质形成细胞趋化因子（GRO/KC）、血管内皮生长因子（VEGF）、单核细胞趋化蛋白-1（MCP-1）、巨噬细胞炎性蛋白-1α（MIP-1α）和IL-17A。在玻璃体中，两种模型中CXCL10、GRO/KC、RANTES和MIP-1α均升高。白细胞介素-17A和IL-18仅在EAU中升高。
致敏分枝杆菌性葡萄膜炎引发急性前、中间葡萄膜炎，不累及视网膜。与EAU相比，致敏分枝杆菌性葡萄膜炎具有独特的促炎细胞因子谱，提示PMU是研究免疫介导性葡萄膜炎的良好补充模型。促炎细胞因子CXCL10在两种模型的房水和玻璃体中均增加，可能是一个可行的治疗靶点。
