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P. Gjorstrup, S. P. Pflugfelder, S. Pangelinan, C. S. De Paiva; Resolvins Protect Against Goblet Cell Loss and Reduce Corneal Epithelial Barrier Disruption in a Murine Model of KCS. Invest. Ophthalmol. Vis. Sci. 2008;49(13):122.
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© ARVO (1962-2015); The Authors (2016-present)
Experimental evidence indicates that omega-3 PUFAs are precursors to potent novel mediators called resolvins. First identified in the resolution phase of inflammatory exudates, later experiments showed that their administration could markedly ameliorate experimentally induced inflammation, whether given prophylactically or therapeutically in rodent disease models. The purpose of this study was to evaluate the potential of resolvin E1 (RvE1, endogenously formed from eicosapentaenoic acid) and its synthetic analog RX-10008 in reducing inflammation and signs of disease in a murine model of dry eye.
Experimental dry eye was created in C57BL/6 mice by subcutaneous scopolamine injection and exposure to an air draft for 5 days, with or without topical therapy, 300 µg/mL of RX-10005 (parent compound RvE1), 300 µg/mL of RX-10065 (parent compound RX-10008) and polysorbate vehicle control, delivered 4 times per day as1 µL drops. Both compounds were administered as their methyl ester prodrugs which in previous experiments were shown to enhance corneal penetration of the parent. Untreated mice were used as controls. Corneal permeability was assessed using Oregon Green Dextran (OGD) staining. Goblet cell density was evaluated by PAS staining.
Desiccating stress caused a marked increase in corneal epithelial permeability to OGD compared to untreated controls ([mean ± SD] 146.50 ± 25.32 vs. 119.3 ± 9.71 gray levels, P<0.05, respectively) and a significant goblet cell loss (4.97 ± 0.88 vs. 6.18 ± 0.86 cells/100 µm, P<0.05, respectively).Topical treatment of eyes with RX-10005 significantly reduced OGD staining compared to vehicle control treated group (122.2 ± 5.9 vs. 135.1 ± 17.04 gray levels, P<0.05, respectively) and also significantly maintained goblet cell density (6.29 ± 0.47 vs. 5.10±0.55 cells/100µm, P<0.05, respectively). In the RX-10065, there was a slight decrease in OGD staining (128.5 ± 17.70 gray levels) but a significant preservation in goblet cell density compared to vehicle group (5.72 ± 0.5, P<0.05).
Our results show that the endogenous resolvin E1 and its analog RX-10008 when administered as methyl ester prodrugs protected against goblet cell loss and also improved corneal barrier function in mice exposed to desiccating stress.
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