Androgen deficiency, meibomian gland dysfunction, and evaporative dry eye
Androgen deficiency, meibomian gland dysfunction, and evaporative dry eye
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DOI：
10.1111/j.1749-6632.2002.tb04217.x
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发表时间：
2002-01-01
期刊：
影响因子：
--
通讯作者：
Dana, MR
中科院分区：
文献类型：
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作者：
Sullivan, DA;Sullivan, BD;Dana, MR
Objective.我们最近发现，原发性和继发性干燥综合征的妇女吃雄激素缺乏。我们假设这种激素不足导致睑板腺功能障碍、泪膜不稳定和蒸发性干眼，这些都是这种自身免疫性疾病的特征。如果我们的假设是正确的，我们预测：（1）雄激素调节睑板腺功能，控制由该组织产生的脂质的质量和/或数量，并促进泪膜脂质层的形成;以及（2）由于雄激素合成的衰减（例如，在干燥综合征、绝经、衰老、完全雄激素不敏感综合征[CAIS]和抗雄激素使用期间），将导致睑板腺功能障碍和蒸发性干眼。以下研究旨在验证这些预测。方法.实验过程包括临床研究、动物模型、组织学、生物化学、分子生物学和生物医学工程技术。结果我们的研究结果表明：（1）雄激素调节睑板腺。该组织含有雄激素受体mRNA、腺泡上皮细胞核内的雄激素受体蛋白以及I型和2型5 α-还原酶mRNA。此外，雄激素似乎调节小鼠和/或兔睑板腺中的脂质产生和基因表达;和（2）雄激素缺乏可能导致睑板腺功能障碍、睑板腺分泌物中脂质分布改变、泪膜不稳定和蒸发性干眼。因此，我们发现男性抗雄激素治疗与睑板腺疾病、泪膜破裂时间缩短和功能性干眼相关。此外，我们发现CAIS女性患者的雄激素受体功能障碍与睑板腺变化以及干眼体征和症状的显著增加相关。有趣的是，我们还发现雄激素缺乏与人睑板腺分泌物的中性和极性脂质模式的显著和惊人的改变有关。结论.我们的研究结果表明，睑板腺是雄激素的靶器官，雄激素缺乏可能会促进睑板腺功能障碍和蒸发性干眼。总之，这些结果支持了我们的假设，雄激素缺乏可能是干燥综合征女性蒸发性干眼发病机制中的一个重要病因。
Objective. We have recently discovered that women with primary and secondary Sjogren's syndrome ate androgen-deficient. We hypothesize that this hormone insufficiency contributes to the meibomian gland dysfunction, tear film instability, and evaporative dry eye that are characteristic of this autoimmune disorder. If our hypothesis is correct, we predict: (1) that androgens regulate meibomian gland function, control the quality and/or quantity of lipids produced by this tissue, and promote the formation of the tear film's lipid layer; and (2) that androgen deficiency, due to an attenuation in androgen synthesis (e.g., during Sjogren's syndrome, menopause, aging, complete androgen-insensitivity syndrome [CAIS] and anti-androgen use), will lead to meibomian gland dysfunction and evaporative dry eye. The following studies were designed to test these predictions. Methods. Experimental procedures included clinical studies, animal models, and histological, biochemical, molecular biological, and biomedical engineering techniques. Results. Our results demonstrate that: (1) androgens regulate the meibomian gland. This tissue contains androgen receptor mRNA, androgen receptor protein within acinar epithelial cell nuclei, and Types I and 2 5alpha-reductase mRNAs. Moreover, androgens appear to modulate lipid production and gene expression in mouse and/or rabbit meibomian glands; and (2) androgen deficiency may lead to meibomian gland dysfunction, altered lipid profiles in meibomian gland secretions, tear film instability, and evaporative dry eye. Thus, we have found that anti-androgen therapy in men is associated with meibomian gland disease, a decreased tear film breakup time, and functional dry eye. Furthermore, we have discovered that androgen receptor dysfunction in women with CAIS is associated with meibomian gland changes and a significant increase in the signs and symptoms of dry eye. Of interest, we have also found that androgen deficiency is associated with significant and striking alterations in the neutral and polar lipid patterns of human meibomian gland secretions. Conclusions. Our findings show that the meibomian gland is an androgen target organ and that androgen deficiency may promote meibomian gland dysfunction and evaporative dry eye. Overall, these results support our hypothesis that androgen deficiency may be an important etiologic factor in the pathogenesis of evaporative dry eye in women with Sjogren's syndrome.