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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Antibodies, Monoclonal / therapeutic use*
  • Burns, Chemical / diagnosis
  • Burns, Chemical / drug therapy*
  • Burns, Chemical / metabolism
  • Corneal Diseases / diagnosis
  • Corneal Diseases / drug therapy*
  • Corneal Diseases / metabolism
  • Cytokines / metabolism
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Eye Burns / chemically induced*
  • Eye Burns / diagnosis
  • Eye Burns / metabolism
  • Hydrogen-Ion Concentration
  • In Situ Nick-End Labeling
  • Infliximab
  • Injections, Intraperitoneal
  • Leukocyte Common Antigens / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Retinal Diseases / diagnosis
  • Retinal Diseases / drug therapy*
  • Retinal Diseases / metabolism
  • Retinal Ganglion Cells / drug effects
  • Retinal Ganglion Cells / metabolism
  • Sodium Hydroxide / toxicity
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Antibodies, Monoclonal
  • Cytokines
  • Tumor Necrosis Factor-alpha
  • Sodium Hydroxide
  • Infliximab
  • Leukocyte Common Antigens
  • Ptprc protein, mouse