Mechanisms of Retinal Damage after Ocular Alkali Burns

Am J Pathol. 2017 Jun;187(6):1327-1342. doi: 10.1016/j.ajpath.2017.02.005. Epub 2017 Apr 13.


Alkali burns to the eye constitute a leading cause of worldwide blindness. In recent case series, corneal transplantation revealed unexpected damage to the retina and optic nerve in chemically burned eyes. We investigated the physical, biochemical, and immunological components of retinal injury after alkali burn and explored a novel neuroprotective regimen suitable for prompt administration in emergency departments. Thus, in vivo pH, oxygen, and oxidation reduction measurements were performed in the anterior and posterior segment of mouse and rabbit eyes using implantable microsensors. Tissue inflammation was assessed by immunohistochemistry and flow cytometry. The experiments confirmed that the retinal damage is not mediated by direct effect of the alkali, which is effectively buffered by the anterior segment. Rather, pH, oxygen, and oxidation reduction changes were restricted to the cornea and the anterior chamber, where they caused profound uveal inflammation and release of proinflammatory cytokines. The latter rapidly diffuse to the posterior segment, triggering retinal damage. Tumor necrosis factor-α was identified as a key proinflammatory mediator of retinal ganglion cell death. Blockade, by either monoclonal antibody or tumor necrosis factor receptor gene knockout, reduced inflammation and retinal ganglion cell loss. Intraocular pressure elevation was not observed in experimental alkali burns. These findings illuminate the mechanism by which alkali burns cause retinal damage and may have importance in designing therapies for retinal protection.

MeSH terms

  • Alkalies
  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology
  • Burns, Chemical / drug therapy
  • Burns, Chemical / etiology
  • Burns, Chemical / metabolism*
  • Burns, Chemical / pathology
  • Cornea / immunology
  • Corneal Injuries / drug therapy
  • Corneal Injuries / etiology
  • Corneal Injuries / metabolism
  • Corneal Injuries / pathology
  • Disease Models, Animal
  • Drug Evaluation, Preclinical / methods
  • Eye Burns / drug therapy
  • Eye Burns / etiology
  • Eye Burns / metabolism*
  • Eye Burns / pathology
  • Hydrogen-Ion Concentration
  • Infliximab / pharmacology
  • Infliximab / therapeutic use
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use
  • Oxidation-Reduction
  • Rabbits
  • Receptors, Tumor Necrosis Factor, Type I / deficiency
  • Receptors, Tumor Necrosis Factor, Type I / genetics
  • Receptors, Tumor Necrosis Factor, Type II / deficiency
  • Receptors, Tumor Necrosis Factor, Type II / genetics
  • Retina / immunology
  • Retina / injuries*
  • Retina / metabolism
  • Retina / pathology
  • Retinal Ganglion Cells / drug effects
  • Retinal Ganglion Cells / pathology
  • Sodium Hydroxide
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / metabolism
  • Uvea / metabolism
  • Uveitis, Anterior / chemically induced
  • Uveitis, Anterior / metabolism
  • Uveitis, Anterior / pathology
  • Uveitis, Anterior / prevention & control


  • Alkalies
  • Neuroprotective Agents
  • Receptors, Tumor Necrosis Factor, Type I
  • Receptors, Tumor Necrosis Factor, Type II
  • Tnfrsf1a protein, mouse
  • Tumor Necrosis Factor-alpha
  • Sodium Hydroxide
  • Infliximab