当前位置： SCI文献检索 > INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE期刊下所有文献 > Contribution of TNF-alpha to leukocyte adhesion, vascular leakage, and apoptotic cell death in endotoxin-induced uveitis in vivo.

Contribution of TNF-alpha to leukocyte adhesion, vascular leakage, and apoptotic cell death in endotoxin-induced uveitis in vivo.

Abstract：

PURPOSE:To investigate the effect of TNF-alpha on leukocyte adhesion, vascular leakage, and apoptotic cell death in endotoxin-induced uveitis (EIU) in the rat. METHODS:EIU was induced in Long-Evans rats by a single footpad injection of lipopolysaccharide (LPS; 350 microg/kg) from Salmonella typhimurium. A single injection of recombinant TNF receptor P75 (etanercept) was given subcutaneously 24 hours before the administration of LPS. Twenty-four hours after administration of LPS, leukocyte adhesion was evaluated in vivo with SLO-acridine orange angiography and ex vivo with concanavalin A lectin staining of retinal flatmounts. Neutrophil activation was quantified by a myeloperoxidase activity assay. Vascular leakage was assessed by Evans blue extravasation. Retinal cell death was assessed with TUNEL staining and quantified with a modified ELISA protocol. Involvement of caspase-3 and -8 was determined by M30 antibody staining, Western blot analysis, and a test for enzymatic activity. RESULTS:Twenty-four hours after the LPS injection, significant increases in leukocyte rolling, adhesion, and activation were observed. In addition, increased levels of apoptosis in the vascular endothelium and the ganglion cell and inner nuclear layers and activation of caspase-8 and -3 were observed. After administration of the TNF-alpha inhibitor, significant reduction in the leukocyte rolling, adhesion, activation, and apoptosis in all the affected layers was observed. The quantitative analysis of vascular leakage revealed a significant decrease after treatment with etanercept. Retinal cell death quantification showed a significant decrease after treatment with the TNF-alpha inhibitor. CONCLUSIONS:Anti-TNF-alpha treatment reduces the LPS-induced increases in leukocyte rolling, adhesion, and vascular leakage in this rat model of inflammatory uveitis. These results suggest the involvement of TNF-alpha in inflammatory uveitis and its potential use as a therapeutic agent in the reduction of ocular inflammation.

journal_name

Invest Ophthalmol Vis Sci

journal_title

Investigative ophthalmology & visual science

authors

Koizumi K,Poulaki V,Doehmen S,Welsandt G,Radetzky S,Lappas A,Kociok N,Kirchhof B,Joussen AM

doi

10.1167/iovs.02-0589

keywords:

subject

Has Abstract

pub_date

2003-05-01 00:00:00

pages

2184-91

issue

eissn

0146-0404

issn

1552-5783

journal_volume

pub_type

杂志文章

在线工具

Contribution of TNF-alpha to leukocyte adhesion, vascular leakage, and apoptotic cell death in endotoxin-induced uveitis in vivo.