Cornea

Skip Navigation LinksHome > April 2014 - Volume 33 - Issue 4 > Alkali Burn to the Eye: Protection Using TNF-α Inhibition
Cornea:
doi: 10.1097/ICO.0000000000000071
Basic Investigation

Alkali Burn to the Eye: Protection Using TNF-α Inhibition

Cade, Fabiano MD, MSc; Paschalis, Eleftherios I. MSc, PhD; Regatieri, Caio V. MD, PhD; Vavvas, Demetrios G. MD, PhD; Dana, Reza MD, MPH, MSc; Dohlman, Claes H. MD, PhD

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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.

© 2014 by Lippincott Williams & Wilkins.

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