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N. Li, J. He, P. Gjorstrup, H. Bazan; The Resolvin E1 Analogs, RX-10065 and RX-10005 Improve Tear Production and Decrease Inflammation in a Mouse Dry Eye Model. Invest. Ophthalmol. Vis. Sci. 2008;49(13):121. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Dry eye (DE) is a common ocular surface disease, particularly among women and elderly population, which can cause eye irritation and blurred vision. Several studies have shown that there is an inflammatory component in DE, although the pathogenesis is not thoroughly understood. Resolvins are mediators derived from the w-3 polyunsaturated fatty acid eicosapentaenoic acid involved in the resolution of inflammation and tissue protection. We investigated the role of two stable analogs of resolvins, RX-10065 and RX-10005 in a mouse DE model.
13 to 14- week-old female BALB/C mice were exposed to desiccating conditions, and 5 ul of 1% atropine was applied topically every other day. One week after DE exposure, the animals were treated with 5 ul of 0.001 % RX10065, 0.001 % RX1005 or vehicle topically 4xday for an additional week. Normal controls (NC) were animals in a normal environment without treatment. Schimer’s test was performed before treatment and at the second and forth day after treatment. Density of corneal epithelial cells was analyzed in vivo using the Rostock Cornea Module of the Heidelberg Retina Tomograph (HRT-II). Corneas were processed for western blot analysis and immunofluorescence examination.
The Schimer’s test showed a significant decrease in tear production in DE (4.8±1.5mm) compared with NC (7.1±1.8mm) (p<0.001). There was no change 2 days and 4 days after treatment with vehicle (4.7±1.2mm, 6.2±2.1mm), but significant increase was observed in the group treated with RX-10005 at 2 days (5.6±1.3mm) and 4 days (7.4±1.2mm). The density of the superficial epithelial cells showed a significant decrease after DE (838.75 ±86 cells/mm2) compared with NC (1072. ±9025 cells/mm2), that increased after RX-10005 and RX-10065 treatment (1043.75±138 cells/mm2 and 1006.5±98 cells/mm2, respectively). Western blot analysis showed that α-SMA and COX-2 were strongly up regulated after DE and decreased with both drugs. Immunofluorescence showed strong positive staining in stroma and/or in epithelium after DE and decrease with treatment.
RX-10065 and RX-10005 significantly increase tear production and inhibited keratocyte transformation to myofibroblasts and the inflammatory inducible COX-2 in these DE mouse model. The results suggest that these resolvin analogs have therapeutic potential in the treatment of DE.
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