Abstract
Purpose: :
Dry Eye Syndrome (DES) is a progressive ocular surface disease characterized by decreased tear gland secretion, altered tear composition, tear film instability and ocular surface inflammation. The condition is more prevalent in women than in men, and androgen-estrogen imbalances are among the hypothesized pathogenic factors. Purpose of this study was to investigate whether supplementation of rats with the isoflavone genistein (GEN) could alleviate artificially induced DES.
Methods: :
24 female Sprague Dawley rats were housed at low humidity and DES was induced by daily trans-dermal treatment with scopolamine (SCOP). The animals were maintained on an AIN feed containing 0 (noGEN), 50 (lowGEN) or 250 ppm (highGEN) of GEN provided as geniVida® by DSM Nutritional Products Ltd. An additional group of 8 animals served as the untreated control group (CON). After 2 and 4 weeks, concentrations of GEN in plasma were measured by LC/MS and the status of DES development was assessed by the Zone Quick Test (ZQT), which determines tear volume by measuring the wetted length of a thread immersed into the lacrimal lake. After four weeks, the animals were sacrificed; cornea and conjunctiva were excised, stained and subjected to analysis of Goblet Cell Density (GCD). Pairwise comparisons of endpoint values were done by t-test or Mann-Whitney test.
Results: :
A substantial systemic exposure to GEN was documented by on average 6 and 38 fold increases of GEN plasma levels in the lowGEN and highGEN groups respectively. The plasma levels reached were comparable to those reported in a human study (Ullmann et al., (2005), Planta Med. 71(10): 891-896). In the noGen group, the ZQT indicated a drastic decrease of tear volume (p=0.023) and the histological evaluation revealed a marked reduction of GCD (p=0.026) in response to SCOP treatment. Supplementing GEN at 50 or 250 ppm significantly improved both tear volume (p=0.00035) and GCD (p=0.0028) to values in the range of the non-treated control group.
Conclusions: :
To our knowledge, these results are the first preclinical demonstration of the efficacy of genistein supplementation to mitigate the effects of Dry Eye Syndrome induced by scopolamine treatment. The effects appear to be due to increased tear volume and restored density of mucus-producing Goblet Cells. If these results could be confirmed in humans under less drastic situations, genistein supplementation could offer an effective systemic treatment for a condition that currently can be managed by palliative topical agents only.
Keywords: cornea: tears/tear film/dry eye • cornea: surface mucins • conjunctiva