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Fang Bian, Crystal S Shin, Stephen C Pflugfelder, Ghanashyam Acharya, Cintia S De Paiva; Dexamethasone Drug Eluting Microwafers Controls Inflammation in Alkali Burned Corneas Associated with Dry Eye. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5621.
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© ARVO (1962-2015); The Authors (2016-present)
To evaluate the efficacy of a controlled release dexamethasone delivery system for suppressing inflammation in a combined model of alkali burn and dry eye.
Microwafers loaded with phosphate Dexamethasone (pDex, 10ug) or vehicle (2.5% Methylcellulose, MC) were fabricated using hydrogel template strategy. Female C57BL/6 mice were subjected to unilateral alkali ocular burn with concomitant desiccating stress for 2 days (D) and topically treated either with 2µL of 0.1% pDex or vehicle (MC) QID and compared to mice that received a single placement of pDex MC-microwafers or blank MC on the cornea after creation of alkali burn. Corneal clarity was graded daily using a 4 point scale. Healing and closure of the epithelial defect was evaluated by 0.1% sodium fluorescein staining and survival curves were generated. Mice were euthanized after 2 days and whole cornea tissues were collected for evaluating gene expression by Real-time PCR.
Wound closure at 2D post injury was noted 84.38% of the pDex drops group which had significantly lower corneal opacity scores compared to its vehicle (2.50±0.29 vs.3.50±0.50, P<0.01). Similar results were seen with the pDex loaded microwafer group. Expression of matrix metalloproteinase (MMPs) and inflammatory cytokines in the mouse cornea are significantly increased in the combined model of alkali burn and dry eye and dramatically down-regulated in the pDex drop and pDex wafer treatment groups at 2D post injury compared with vehicle controls. pDex drop treatment significantly decreased mRNA expression levels of IL-1β (19 vs. 4 fold), IL-6 (28 vs. 18 fold), MMP-1 (34 vs.17 fold), MMP-9 (140 vs. 4 fold) and MMP-13 (9 vs. 3 fold) and increased MMP-8 (652 vs.112 fold) compared to MC drops after 2 days of initial lesion. Compared to blank wafers, pDex microwafers significantly decreased mRNA expression levels of IL-1β (21 vs. 10 fold), IL-6 (38 vs. 19 fold), MMP-1 (22 vs. 19 fold), MMP-3 (10 vs.3 fold), MMP-9 (24 vs. 10 fold) and MMP-13 (7 vs. 4 fold) while increased MMP-8 (150 vs. 44 fold) mRNA transcripts.
A single Dexamethasone-loaded microwafer is equally efficacious as conventional Dexamethasone drops in preserving corneal clarity and decreasing expression of MMPs and inflammatory cytokines of the cornea in a combined model of alkali burn and dry eye.
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