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Boston Type I 角膜假体患者的肿瘤坏死因子-α及其 II 型受体的血液水平升高。

Blood Levels of Tumor Necrosis Factor Alpha and Its Type 2 Receptor Are Elevated in Patients with Boston Type I Keratoprosthesis.

机构信息

a Department of Ophthalmology , Harvard Medical School, Massachusetts Eye and Ear , Boston , MA , USA.

b Boston Keratoprosthesis Laboratory , Massachusetts Eye and Ear - Schepens Eye Research Institute, Harvard Medical School , Boston , MA , USA.

出版信息

Curr Eye Res. 2019 Jun;44(6):599-606. doi: 10.1080/02713683.2019.1568500. Epub 2019 Feb 4.

Abstract

: Boston keratoprosthesis (KPro) patients are prone to glaucoma even with well-controlled intraocular pressure (IOP). Recent experimental data have shown that soluble tumor necrosis factor alpha (TNF-) after ocular injury may contribute to progressive retinal damage and subsequent glaucoma. This study evaluates the blood plasma levels of soluble TNF-, TNF receptors 1 (TNFR1) and 2 (TNFR2), and leptin in patients with Boston type I KPro. : Venous blood samples were collected from KPro patients with glaucoma (KPro G, = 19), KPro patients without glaucoma (KPro NoG, = 12), primary angle closure glaucoma without KPro (PACG, = 13), and narrow angles without glaucoma or KPro (NA, = 21). TNF-, TNFR1, TNFR2, and leptin levels were quantified using the enzyme-linked immunosorbent assay. Erythrocyte sedimentation rate (ESR) was assessed using the Westergren test. Patients with underlying autoimmune conditions or diabetes were excluded from the study. : All groups had similar age, body mass index (BMI), IOP, and ESR ( ≥ 0.11). The mean time from KPro surgery to blood draw was 5.3 ± 3.7 years. Compared to NA patients (0.72 ± 0.3 pg/ml), KPro G and KPro NoG patients had higher blood plasma levels of TNF- (1.18 ± 0.58 pg/ml, = 0.006; 1.16 ± 0.50 pg/ml, = 0.04, respectively). Similarly, KPro G patients had higher blood plasma levels of TNFR2 (2768 ± 1368 pg/ml) than NA patients (2020 ± 435 pg/ml, = 0.048). In multivariate analysis, KPro status remained positively associated with TNF- levels ( = 0.36; 95% confidence intervals [CI]: 0.14-0.58; = 0.002) and TNFR2 levels ( = 458.3; 95% CI: 32.8-883.7; = 0.035) after adjusting for age, gender, BMI, glaucoma status, and ESR. TNFR1 and leptin levels were not significantly different in the study groups. : We detected elevated serum levels of TNF- and TNFR2 in KPro patients. Longitudinal studies are needed to establish TNF- and TNFR2 as serum biomarkers related to KPro surgery. : BCVA: best corrected visual acuity; BMI: body mass index; CDR: cup-to-disc ratio; EDTA: ethylenediaminetetraacetic acid; ELISA: enzyme-linked immunosorbent assay; ESR: erythrocyte sedimentation rate; HVF: Humphrey visual field; IOP: intraocular pressure; KPro G: keratoprosthesis with glaucoma; KPro NoG: keratoprosthesis without glaucoma; KPro: keratoprosthesis; MD: mean deviation; NA: narrow angle; non-KPro: without keratoprosthesis; PACG: primary angle closure glaucoma; RNFL: retinal nerve fiber layer; TNF-α: tumor necrosis factor alpha; TNFR1: tumor necrosis factor receptor 1; TNFR2: tumor necrosis factor receptor 2.

摘要

波士顿角膜(KPro)患者即使眼压(IOP)得到良好控制,也易患青光眼。最近的实验数据表明,眼损伤后可溶性肿瘤坏死因子-α(TNF-)可能导致进行性视网膜损伤和随后的青光眼。本研究评估了波士顿 I 型 KPro 患者的血浆可溶性 TNF-、TNF 受体 1(TNFR1)和 2(TNFR2)和瘦素水平。

静脉血取自青光眼 KPro 患者(KPro G, = 19)、无青光眼 KPro 患者(KPro NoG, = 12)、原发性闭角型青光眼无 KPro(PACG, = 13)和无青光眼或 KPro 窄角(NA, = 21)。采用酶联免疫吸附试验定量检测 TNF-、TNFR1、TNFR2 和瘦素水平。采用 Westergren 试验检测红细胞沉降率(ESR)。排除有自身免疫性疾病或糖尿病的患者。

所有组的年龄、体重指数(BMI)、IOP 和 ESR(≥0.11)均相似。从 KPro 手术到采血的平均时间为 5.3±3.7 年。与 NA 患者(0.72±0.3pg/ml)相比,KPro G 和 KPro NoG 患者的血浆 TNF-水平更高(1.18±0.58pg/ml, = 0.006;1.16±0.50pg/ml, = 0.04)。同样,KPro G 患者的血浆 TNFR2 水平(2768±1368pg/ml)高于 NA 患者(2020±435pg/ml, = 0.048)。在多变量分析中,调整年龄、性别、BMI、青光眼状态和 ESR 后,KPro 状态与 TNF-水平( = 0.36;95%置信区间[CI]:0.14-0.58; = 0.002)和 TNFR2 水平( = 458.3;95%CI:32.8-883.7; = 0.035)呈正相关。研究组中 TNFR1 和瘦素水平无显著差异。

我们在 KPro 患者中检测到血清 TNF-和 TNFR2 水平升高。需要进行纵向研究以确定 TNF-和 TNFR2 是否为与 KPro 手术相关的血清生物标志物。

BCVA

最佳矫正视力;BMI:体重指数;CDR:杯盘比;EDTA:乙二胺四乙酸;ELISA:酶联免疫吸附试验;ESR:红细胞沉降率;HVF:Humphrey 视野;IOP:眼内压;KPro G:青光眼角膜;KPro NoG:无青光眼角膜;KPro:角膜;MD:平均偏差;NA:窄角;非 KPro:无角膜;PACG:原发性闭角型青光眼;RNFL:视网膜神经纤维层;TNF-α:肿瘤坏死因子-α;TNFR1:肿瘤坏死因子受体 1;TNFR2:肿瘤坏死因子受体 2。

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