眼部碱烧伤：使用 TNF-α 抑制进行保护。

Alkali burn to the eye: protection using TNF-α inhibition.

机构信息

Department of Ophthalmology, Cornea Service, Angiogenesis Laboratory, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA.

出版信息

Cornea. 2014 Apr;33(4):382-9. doi: 10.1097/ICO.0000000000000071.

DOI:10.1097/ICO.0000000000000071

PMID:24488127

Abstract

PURPOSE

The aim of this study was to evaluate early retinal damage after induction of ocular surface alkali burns and the protective effects of tumor necrosis factor alpha (TNF-α) blockade.

METHODS

Alkali injury was induced in mouse corneas by using 1 N NaOH. Retinal damage was assessed using a terminal deoxynucleotidyl transferase 2'-deoxyuridine 5-triphosphate nick end labeling (TUNEL) assay, 15 minutes to 14 days postburn. Immune cell infiltration was assessed by CD45 immunolocalization. Retinal cytokines were quantified using the enzyme-linked immunosorbent assay for interleukin (IL)1β, IL2, IL6, TNF-α, CCL5, and macrophage inflammatory protein-1α. Protection against retinal damage was attempted with a single dose of either anti-TNF-α antibody (infliximab, 6.25 mg/kg) or control immunoglobulin G (IgG), administered intraperitoneally 15 minutes after the burn was inflicted. Corneal injury was evaluated by using TUNEL and CD45 immunolocalization and by quantifying corneal neovascularization.

RESULTS

There was significant damage to the retina within 24 hours of the corneal burn being inflicted. TUNEL+ labeling was present in 80% of the retinal ganglion cells, including a few CD45+ cells. There was a 10-fold increase in the retinal inflammatory cytokines in the study groups compared with that in controls. A single intraperitoneal dose of anti-TNF-α antibody, administered 15 minutes after the burn, markedly reduced retinal TUNEL+, CD45+ labeling, and inflammatory cytokine expression, compared with that in the controls. Additionally, TNF-α blockade caused a marked reduction in corneal neovascularization, and in cornea TUNEL and CD45 labeling, 5 days after the burn.

CONCLUSIONS

This study shows that alkali corneal burns can induce significant retinal damage within 24 hours. A single dose of anti-TNF-α antibody, administered 15 minutes after inflicting the burn, provides significant retinal and corneal protection. This could lead to the discovery of novel therapies for patients with alkali injuries.

摘要

目的

本研究旨在评估诱导眼表碱烧伤后早期视网膜损伤及肿瘤坏死因子α（TNF-α）阻断的保护作用。

方法

用 1N NaOH 诱导小鼠角膜碱烧伤。伤后 15 分钟至 14 天，采用末端脱氧核苷酸转移酶 2'-脱氧尿苷 5'-三磷酸末端标记（TUNEL）法评估视网膜损伤。通过 CD45 免疫定位评估免疫细胞浸润。采用酶联免疫吸附试验检测白细胞介素（IL）1β、IL2、IL6、TNF-α、CCL5 和巨噬细胞炎症蛋白-1α 等视网膜细胞因子。伤后 15 分钟，经腹腔注射单次剂量抗 TNF-α 抗体（英夫利昔单抗，6.25mg/kg）或对照免疫球蛋白 G（IgG），试图对视网膜损伤进行保护。采用 TUNEL 和 CD45 免疫定位及定量检测角膜新生血管化，评估角膜损伤。

结果

角膜烧伤后 24 小时内视网膜明显受损。TUNEL+标记见于 80%的视网膜神经节细胞，其中少数为 CD45+细胞。与对照组相比，研究组视网膜炎症细胞因子增加了 10 倍。伤后 15 分钟经腹腔注射单次剂量抗 TNF-α 抗体，与对照组相比，显著减少视网膜 TUNEL+、CD45+标记及炎症细胞因子表达。此外，TNF-α 阻断导致烧伤后 5 天角膜新生血管化、角膜 TUNEL 和 CD45 标记显著减少。