Journal
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
Volume 57, Issue 7, Pages 3222-3230Publisher
ASSOC RESEARCH VISION OPHTHALMOLOGY INC
DOI: 10.1167/iovs.16-19074
Keywords
nanowafer; alkali injury; dry eye; neutrophils; MMPs; dexamethasone
Categories
Funding
- National Institutes of Health (NIH
- Bethesda, MD, USA) Training Grant [T32-AI053831]
- National Eye Institute/NIH Core Grant [EY-002520]
- Research to Prevent Blindness (New York, NY, USA)
- Oshman Foundation (Houston, TX, USA)
- William Stamps Farish Fund (Houston, TX, USA)
- Hamill Foundation (Houston, TX, USA)
- [W81XWH-12-1-0616]
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PURPOSE. To evaluate the efficacy of a controlled release dexamethasone delivery system for suppressing inflammation in an ocular burn + desiccating stress (OB+DS) model. METHODS. Nanowafers (NW) loaded with Dexamethasone (Dex, 10 mu g) or vehicles (2.5% Methylcellulose; MC) were fabricated using hydrogel template strategy. C57BL/6 mice were subjected to unilateral alkali ocular burn with concomitant desiccating stress for 2 or 5 days and topically treated either with 2 mu L of 0.1 % Dex or vehicle four times per day and compared with mice that had MC-NW or Dex-NW placed on their corneas. Clinical parameters were evaluated daily. Mice were euthanized after 2 or 5 days. Quantitative PCR evaluated the expression of inflammatory cytokines IL-beta and IL-6 and matrix metalloproteinases (MMP) in whole cornea lysates. Myeloperoxidase activity (MPO) was measured using a commercial kit in cornea lysates. RESULTS. Both Dex drop and Dex-NW groups had significantly lower corneal opacity scores compared with their vehicles. Both Dex drops and Dex-NW significantly decreased expression of IL-1 beta, IL-6, and MMP-9 RNA transcripts compared with vehicle drops or wafers 2 and 5 days after the initial lesion. A significant lower number of neutrophils was found in both Dex treatment groups and this was accompanied by decreased MPO activity compared with vehicle controls. CONCLUSIONS. Dex-NW has efficacy equal to Dex drops in preserving corneal clarity and decreasing expression of MMPs and inflammatory cytokines of the corneas of mice subjected to an OB+DS model.
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