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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

doi: 10.1097/ICO.0000000000000071
Basic Investigation

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.

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

Reprints: Eleftherios I. Paschalis, Department of Ophthalmology, Cornea Service, Massachusetts Eye and Ear Infirmary, Harvard Medical School, 243 Charles St, Boston 02114, MA (e-mail:

Supported by the Boston Keratoprosthesis Research Fund, Massachusetts Eye and Ear Infirmary, Boston, MA.

The authors have no funding or conflicts of interest to disclose.

F. Cade and E. I. Paschalis contributed equally to this study.

Received June 07, 2013

Accepted December 19, 2013

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