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Cintia De Paiva, Flavia Pelegrino, Eugene Volpe, Stephen Pflugfelder; Anti-inflammatory therapy changes fate of alkali burned corneas associated with dry eye. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5980.
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The purpose of this study was to investigate the effects of anti-inflammatory therapy in a concomitant dry eye and corneal alkali burn murine model.
C57BL/6 mice were subjected to unilateral alkali ocular burn (OB) without or with concomitant desiccating stress (DS) for 2 or 5 days (D). A separate group of mice that received both OB and DS were topically treated either with 2µL Dexamethasone, 2uL of Doxycycline or vehicle (balanced salt solution). Mice were observed daily for appearance of corneal perforation. Mice were euthanized after 2 or 5 days and eyes and adnexa were collected for histology. Whole corneas were collected and lysed for gene expression. Quantitative real time PCR was performed to measure expression of inflammation cytokines and matrix metalloproteinases (MMPs).
Eyes subjected to OB+DS had 20% sterile corneal perforation rate as soon as 1 day after the initiation of the insults which increased to 80%-90% by 5 days; significantly increased MMP-9 immunoreactivity and activity were noted compared to OB and DS controls. Significantly increased MMP-1,-3,-8,-9, -13, IL-1β and IL-6 mRNA transcripts in cornea were found early at day 2 in OB+DS compared to OB alone. OB+DS eyes treated with Doxycycline or Dexamethasone had significant lower rate of ocular perforation (10% at 2D, 20% at 5D and 0% at 2 and 5D, respectively), and significantly decreased MMP-1,-3, -8, -9, IL-1β and IL-6 mRNA transcripts in cornea compared to vehicle-treated eyes.
Concomitant dry eye and alkali burn leads to ocular perforation accompanied by cytokine and MMP storm in the cornea. Early treatment with anti-inflammatory therapy is critical in preserving eye integrity and decreasing IL-1β, IL-6 and MMPs.
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