Herbert Wertheim School of Optometry & Vision Science, University of California, Berkeley, California, United States.
Department of Molecular and Cell Biology and Helen Wills Neuroscience Institute, University of California, Berkeley, California, United States.
Invest Ophthalmol Vis Sci. 2023 Aug 1;64(11):21. doi: 10.1167/iovs.64.11.21.
Contact lens wear can induce corneal parainflammation involving CD11c+ cell responses (24 hours), γδ T cell responses (24 hours and 6 days), and IL-17-dependent Ly6G+ cell responses (6 days). Topical antibiotics blocked these CD11c+ responses. Because corneal CD11c+ responses to bacteria require transient receptor potential (TRP) ion-channels (TRPA1/TRPV1), we determined if these channels mediate lens-induced corneal parainflammation.
Wild-type mice were fitted with contact lenses for 24 hours or 6 days and compared to lens wearing TRPA1 (-/-) or TRPV1 (-/-) mice or resiniferatoxin (RTX)-treated mice. Contralateral eyes were not fitted with lenses. Corneas were examined for major histocompatibility complex (MHC) class II+, CD45+, γδ T, or TNF-α+ cell responses (24 hours) or Ly6G+ responses (6 days) by quantitative imaging. The quantitative PCR (qPCR) determined cytokine gene expression.
Lens-induced increases in MHC class II+ cells after 24 hours were abrogated in TRPV1 (-/-) but not TRPA1 (-/-) mice. Increases in CD45+ cells were unaffected. Increases in γδ T cells after 24 hours of wear were abrogated in TRPA1 (-/-) and TRPV1 (-/-) mice, as were 6 day Ly6G+ cell responses. Contralateral corneas of TRPA1 (-/-) and TRPV1 (-/-) mice showed reduced MHC class II+ and γδ T cells at 24 hours. RTX inhibited lens-induced parainflammatory phenotypes (24 hours and 6 days), blocked lens-induced TNF-α and IL-18 gene expression, TNF-α+ cell infiltration (24 hours), and reduced baseline MHC class II+ cells.
TRPA1 and TRPV1 mediate contact lens-induced corneal parainflammation after 24 hours and 6 days of wear and can modulate baseline levels of resident corneal immune cells.
隐形眼镜佩戴可引起角膜副炎症反应，涉及 CD11c+细胞反应（24 小时）、γδ T 细胞反应（24 小时和 6 天）以及依赖于白细胞介素-17 的 Ly6G+细胞反应（6 天）。局部抗生素可阻断这些 CD11c+反应。由于角膜对细菌的 CD11c+反应需要瞬时受体电位（TRP）离子通道（TRPA1/TRPV1），我们确定这些通道是否介导隐形眼镜引起的角膜副炎症反应。
野生型小鼠佩戴隐形眼镜 24 小时或 6 天，并与佩戴隐形眼镜的 TRPA1（-/-）或 TRPV1（-/-）小鼠或树脂毒素（RTX）处理的小鼠进行比较。对侧眼睛不佩戴隐形眼镜。通过定量成像检查角膜主要组织相容性复合物（MHC）II 类+、CD45+、γδ T 或 TNF-α+细胞反应（24 小时）或 Ly6G+反应（6 天）。定量聚合酶链反应（qPCR）确定细胞因子基因表达。
24 小时后，隐形眼镜诱导的 MHC Ⅱ类+细胞增加在 TRPV1（-/-）但不是 TRPA1（-/-）小鼠中被消除。CD45+细胞增加不受影响。佩戴隐形眼镜 24 小时后，γδ T 细胞增加在 TRPA1（-/-）和 TRPV1（-/-）小鼠中被消除，6 天后 Ly6G+细胞反应也被消除。TRPA1（-/-）和 TRPV1（-/-）小鼠的对侧角膜在 24 小时时显示 MHC Ⅱ类+和 γδ T 细胞减少。RTX 抑制隐形眼镜引起的副炎症表型（24 小时和 6 天），阻断隐形眼镜诱导的 TNF-α和白细胞介素-18 基因表达、TNF-α+细胞浸润（24 小时），并减少基线 MHC Ⅱ类+细胞。
TRPA1 和 TRPV1 介导佩戴隐形眼镜 24 小时和 6 天后角膜的副炎症反应，并可调节角膜常驻免疫细胞的基线水平。
