An in vivo study of anti-inflammatory effect of Quercetin and Resveratrol polyphenols in a desiccating stress mouse model of dry eye.

Abstract

Purpose: To determine the anti-inflammatory effect of two polyphenols, quercetin (QCT) and resveratrol (RES), and a combination (QCT+RES) in a mouse model of dry eye.

Methods: Dry eye was induced in female C57BL/6 mice exposing them to a desiccating stress (DS): 23°C, 20% relative humidity, constant airflow and subcutaneous scopolamine administration 0.1 mg/d for 10 days. QCT, RES, QCT+RES or vehicle were applied topically 3 times a day starting day -1. Non exposure and untreated mice were used as controls. CD4⁺ T cells isolated from DS and control mice were transferred to nude C57BL/6 recipient mice and were evaluated after 3 days of transfer. Tear production, conjunctival goblet cells density, CD4⁺ T cell infiltration in conjunctiva and cytokine production in tears were evaluated in DS, control and recipient mice at the end of the assay. Corneal fluorescein staining (CFS) was performed in control and DS mice. Cytokine production in tears was additionally evaluated at day 6 in DS mice.

Results: DS altered the ocular surface increasing CFS after 10 days. This effect was decreased by QCT (P<0.001) and QCT+RES (P<0.05) treatments, compared to vehicle. DS provoked an increase in tear levels of IL-1α and RANTES after 6 days of exposure. QCT, RES and QCT+RES treatment significantly decreased IL-1α levels in tears compared to vehicle, (P<0.05, 0.01 and 0.01, respectively). Neither QCT, RES or the combination had any effect on tear production, goblet cell density and CD4⁺ T cell infiltration in DS mice. However, a significant increase in tear production (P<0.01) was found in recipients of QCT+RES treated mice, compared to recipients of vehicle. Moreover, CD4⁺ T cell infiltration in conjunctiva was found to be significantly lower (P<0.05) in recipients of RES treated mice, compared to that observed in recipients of vehicle mice. Cytokine production in tears and goblet cell density in recipient mice were not affected by polyphenols treatments.

Conclusions: Topical treatment with QCT, RES or QCT+RES reduced several inflammatory changes and clinical signs in an experimental mouse dry eye model, decreasing IL-1α production in tears and corneal staining in DS mice, and tear production and CD4⁺ T cell conjunctival infiltration in recipient mice. These results suggest that the topical application of both compounds could be used for the treatment of dry eye.

Keywords: 486 cornea: tears/tear film/dry eye • 557 inflammation • 490 cytokines/chemokines