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Blood‐retinal barrier (BRB) breakdown in experimental autoimmune uveoretinitis: Comparison with vascular endothelial growth factor, tumor necrosis factor α, and interleukin‐1β‐mediated breakdown
Author(s) -
Luna Jose D.,
Chan ChiChao,
Derevjanik Nancy L.,
Mahlow Jeremy,
Chiu Charlie,
Peng Bo,
Tobe Takao,
Campochiaro Peter A.,
Vinores Stanley A.
Publication year - 1997
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/(sici)1097-4547(19970801)49:3<268::aid-jnr2>3.0.co;2-a
Subject(s) - extravasation , tight junction , tumor necrosis factor alpha , blood–retinal barrier , retinal , retina , immunology , medicine , inflammation , biology , pathology , microbiology and biotechnology , endocrinology , ophthalmology , diabetic retinopathy , neuroscience , diabetes mellitus
Experimental autoimmune uveoretinitis (EAU) induced in Lewis rats by immunization with S‐antigen is a model of human uveitis. By using immunocytochemical staining for albumin, relatively minor blood‐retinal barrier (BRB) breakdown was initially shown in the peripheral retina 8 days after immunization and in the posterior retina by 10 days. Albumin extravasation appeared to occur by opening of the retinal vascular endothelial (RVE) and the retinal pigmented epithelial (RPE) tight junctions, by transendothelial vesicular transport, and by permeating damaged RVE cells. Each of three anti‐inflammatory agents reduced or delayed autoimmune‐mediated cell destruction but did not eliminate any particular route of extravasation. Vascular endothelial growth factor (VEGF), tumor necrosis factor α (TNFα), and interleukin‐1 β (IL‐1 β ) are intimately associated with the development of EAU and are capable of causing BRB dysfunction. A high percentage of RVE tight junctions appeared open ultrastructurally after intravitreal injection of VEGF (26.7%), TNFα (35.6%), or IL‐1 β (22.1%) compared with saline‐injected control (11.4%) or normal, untreated rabbits (4.1%). Heat treatment abolished the effect of IL‐1 β on the BRB but only partially reduced the effect of VEGF. By 24 hr after injection, the effect of TNFα had reversed, but that of IL‐1 β had not; VEGF‐mediated BRB dysfunction was partially reversible. In addition, albumin‐filled vesicle‐like structures were seen in the RVE cytoplasm following treatment with each mediator. This study shows that VEGF, TNFα, and IL‐1 β each cause BRB breakdown by opening tight junctions between RVE cells and possibly by increasing transendothelial vesicular transport. Each of these agents may contribute to BRB breakdown in EAU and in patients with uveitis. J. Neurosci. Res. 49:268–280, 1997. © 1997 Wiley‐Liss, Inc.