色素播散有助于色素性青光眼 DBA/2J 小鼠模型中的眼免疫赦免。

Pigment Dispersion Contributes to Ocular Immune Privilege in a DBA/2J Mouse Model of Pigmentary Glaucoma.

机构信息

Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical, University, Beijing Ophthalmology and Visual Sciences Key Lab, Beijing, P. R. China.

出版信息

Invest Ophthalmol Vis Sci. 2024 Jul 1;65(8):51. doi: 10.1167/iovs.65.8.51.

DOI:10.1167/iovs.65.8.51

PMID:39083309

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11290564/

Abstract

PURPOSE

To investigate the effects of anterior chamber pigment dispersion on ocular immune privilege and the possible mechanisms involved in a DBA/2J mouse model of pigmentary glaucoma.

METHODS

DBA/2J mice were utilized as a pigment dispersion model, and age-matched C57BL/6J mice were used as the control group in this study. Proteins in the aqueous humor (AH) and serum were quantified using the bicinchoninic acid assay. Immune cells in the AH were detected using hematoxylin and eosin staining and immunocytochemistry. The expression of TGF-β2 in the AH and cytokine levels (IL-10, IFN-γ) in serum were measured using ELISA. Anterior chamber-associated immune deviation (ACAID) was induced in DBA/2J mice by injecting antigens into the anterior chamber. Delayed-type hypersensitivity (DTH) assays were used to assess the induction of ACAID. In DBA/2J mice, before and after pigment dispersion, following anterior chamber injection of pigment particles, and after ACAID modeling, the expression of regulatory T cells (Tregs) was detected using flow cytometry.

RESULTS

Compared to C57BL/6J mice, the protein concentration, immune cell count, and TGF-β2 levels in the AH were elevated in DBA/2J mice. Protein concentration and IL-10 levels in serum were increased, while IFN-γ levels were decreased in DBA/2J. Additionally, the expression of Treg cells in the spleen of DBA/2J mice was significantly increased after pigment dispersion and anterior chamber injection of pigment particles. At 3 and 6 months, DTH responses in DBA/2J mice were not inhibited, thus preventing ACAID induction. However, the opposite was observed at 9 months in DBA/2J mice. Furthermore, the ACAID group exhibited an augmented expression of Treg cells.

CONCLUSIONS

Dispersion of pigment particles in the anterior chamber of the eye enhances the state of ocular immune privilege by influencing the immunosuppressive microenvironment and inducing more Treg cells to reestablish ACAID.

摘要

目的

研究眼前房色素弥散对眼免疫赦免的影响及其在 DBA/2J 色素性青光眼模型中的可能机制。

方法

本研究采用 DBA/2J 小鼠作为色素弥散模型，以年龄匹配的 C57BL/6J 小鼠作为对照组。采用双缩脲法检测房水中的蛋白质含量，用苏木精-伊红染色和免疫细胞化学检测房水中的免疫细胞。采用 ELISA 检测房水中 TGF-β2 的表达和血清中细胞因子（IL-10、IFN-γ）水平。采用前房注射抗原诱导 DBA/2J 小鼠眼前房相关免疫偏离（ACAID）。采用迟发型超敏反应（DTH）检测评估 ACAID 的诱导。在 DBA/2J 小鼠中，在眼前房色素颗粒注射前后、ACAID 建模前后，通过流式细胞术检测调节性 T 细胞（Treg）的表达。

结果

与 C57BL/6J 小鼠相比，DBA/2J 小鼠房水中的蛋白质浓度、免疫细胞计数和 TGF-β2 水平升高，血清中蛋白质浓度和 IL-10 水平升高，IFN-γ水平降低。此外，DBA/2J 小鼠眼前房色素颗粒注射后脾中 Treg 细胞的表达明显增加。在 3 个月和 6 个月时，DBA/2J 小鼠的 DTH 反应未被抑制，从而防止了 ACAID 的诱导。然而，在 9 个月时，DBA/2J 小鼠的情况则相反。此外，ACAID 组 Treg 细胞的表达增强。