Department of Cornea and Refractive Surgery, Narayana Nethralaya, Bangalore, India.
GROW Research Laboratory, Narayana Nethralaya Foundation, 3rd Floor, Narayana Nethralaya, #258/A Hosur Road, Bommasandra, Bangalore, 560099, India.
Sci Rep. 2021 Oct 22;11(1):20891. doi: 10.1038/s41598-021-99805-9.
Inflammatory factors have been considered to contribute to keratoconus (KC) pathogenesis. This study aims to determine the immune cells subsets and soluble inflammatory factor profile on the ocular surface of KC patients. 32 KC subjects (51 eyes) across different grades of severity and 15 healthy controls (23 eyes) were included in the study. Keratometry and pachymetry measurements were recorded. Ocular surface immune cells (collected by ocular surface wash) immunophenotyped using flow cytometry include leukocytes, neutrophils, macrophages, natural killer (NK) cells, pan-T cells, gamma delta T (γδT) cells and NKT cells. Tear fluid collected using Schirmer's strip was used to measure 50 soluble factors by multiplex ELISA. Proportions of activated neutrophils, NK cells and γδT cells were significantly increased in KC patients. Significantly higher levels of tear fluid IL-1β, IL-6, LIF, IL-17A, TNFα, IFNα/β/γ, EPO, TGFβ1, PDGF-BB, sVCAM, sL-selectin, granzyme-B, perforin, MMP2, sFasL and IgE, along with significantly lower levels of IL-1α and IL-9 were observed in KC patients. Alterations observed in few of the immuno-inflammatory parameters correlated with grades of disease, allergy, eye rubbing and keratometry or pachymetry measurements. The observation implies a distinct immuno-inflammatory component in KC pathogenesis and its potential as an additional therapeutic target in KC management.
炎症因子被认为与圆锥角膜(KC)的发病机制有关。本研究旨在确定 KC 患者眼表的免疫细胞亚群和可溶性炎症因子谱。研究纳入了 32 名 KC 患者(51 只眼)和 15 名健康对照者(23 只眼),这些患者的严重程度不同。记录角膜曲率计和角膜测厚仪测量值。使用流式细胞术对眼表免疫细胞(通过眼表冲洗收集)进行免疫表型分析,包括白细胞、中性粒细胞、巨噬细胞、自然杀伤(NK)细胞、泛 T 细胞、γδT 细胞和 NKT 细胞。使用 Schirmer 条收集的泪液用于通过多重 ELISA 测量 50 种可溶性因子。KC 患者中活化的中性粒细胞、NK 细胞和 γδT 细胞的比例显著增加。KC 患者的泪液中白细胞介素 1β(IL-1β)、白细胞介素 6(IL-6)、白血病抑制因子(LIF)、白细胞介素 17A(IL-17A)、肿瘤坏死因子-α(TNFα)、干扰素-α/β/γ(IFNα/β/γ)、促红细胞生成素(EPO)、转化生长因子-β1(TGFβ1)、血小板衍生生长因子-BB(PDGF-BB)、可溶性血管细胞黏附分子-1(sVCAM-1)、可溶性 L-选择素(sL-selectin)、颗粒酶 B(granzyme-B)、穿孔素、基质金属蛋白酶 2(MMP2)、可溶性 Fas 配体(sFasL)和 IgE 的水平显著升高,而 IL-1α 和 IL-9 的水平显著降低。在少数免疫炎症参数中观察到的改变与疾病严重程度、过敏、揉眼和角膜曲率计或角膜测厚仪测量值相关。该观察结果意味着在 KC 的发病机制中存在明显的免疫炎症成分,并且可能成为 KC 治疗管理中的另一个治疗靶点。