You In-Cheon, Bian Fang, Volpe Eugene A, de Paiva Cintia S, Pflugfelder Stephen C
Department of Ophthalmology, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute, Chonbuk National University Hospital, Jeonju, Jeonbuk, Korea 2Ocular Surface Center, Department of Ophthalmology, Cullen Eye.
Ocular Surface Center, Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, Texas, United States.
Invest Ophthalmol Vis Sci. 2015 Apr;56(4):2224-33. doi: 10.1167/iovs.14-15668.
To investigate parameters of ocular surface disease in C57BL/6.NOD-Aec1Aec2 (Aec) mice with aging and their correlation with development of Sjögren syndrome (SS)-like lacrimal gland (LG) disease.
Aec and C57BL/6 wild-type (B6) female mice were evaluated at 4, 12, and 20 weeks of age. Whole LG and eyes and adnexa were excised for histology and gene expression analysis and evaluated by flow cytometry and immunohistochemistry. Tear volume and goblet cell density was measured. Quantitative PCR evaluated T-cell-related cytokine expression in cornea and conjunctiva.
Both strains showed age-related conjunctival goblet cell loss that was more pronounced in the Aec strain and significantly greater than in B6 mice at 12 weeks. This was accompanied by CD4+ T-cell infiltration of the conjunctiva that was greater in Aec strain at 20 weeks. Aec mice had higher levels of IL-17A, IL-17R, IL-1α, IL-1β, and TNF-α in the conjunctiva, and they significantly increase with aging. Aec mice had greater lymphocytic infiltration of the LG and conjunctiva at 20 weeks that consisted of a mixture of CD4+ and CD8+ cells. Flow cytometry showed a significant increase in CD4+ T cells in Aec LG compared to B6 mice. Tear volume was significantly increased in both strains at 20 weeks.
Aec mice developed greater conjunctival goblet cell loss associated with lymphocytic infiltration of the LG and conjunctiva with aging. Increased expression of certain T helper or inflammatory cytokines in these tissues was observed in Aec mice. The conjunctival disease appeared to be due to inflammation and not a decrease in tear volume.
研究C57BL/6.NOD-Aec1Aec2（Aec）小鼠眼表疾病参数随年龄的变化及其与干燥综合征（SS）样泪腺（LG）疾病发展的相关性。
对4周、12周和20周龄的Aec和C57BL/6野生型（B6）雌性小鼠进行评估。切除整个泪腺、眼睛及附属器用于组织学和基因表达分析，并通过流式细胞术和免疫组织化学进行评估。测量泪液量和杯状细胞密度。采用定量PCR评估角膜和结膜中T细胞相关细胞因子的表达。
两种品系均出现与年龄相关的结膜杯状细胞丢失，在Aec品系中更为明显，且在12周龄时显著高于B6小鼠。这伴随着结膜CD4+ T细胞浸润，在20周龄时Aec品系中更为明显。Aec小鼠结膜中IL-17A、IL-17R、IL-1α、IL-1β和TNF-α水平较高，且随年龄显著增加。20周龄时，Aec小鼠泪腺和结膜的淋巴细胞浸润更严重，由CD4+和CD8+细胞混合组成。流式细胞术显示，与B6小鼠相比，Aec泪腺中CD4+ T细胞显著增加。20周龄时，两种品系的泪液量均显著增加。
随着年龄增长，Aec小鼠结膜杯状细胞丢失更严重，伴有泪腺和结膜的淋巴细胞浸润。在Aec小鼠的这些组织中观察到某些辅助性T细胞或炎性细胞因子的表达增加。结膜疾病似乎是由炎症引起的，而非泪液量减少。
