Department of Ophthalmology, Keio University School of Medicine, Tokyo, 160-8582, Japan.
Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, 160-8582, Japan.
Sci Rep. 2019 Mar 4;9(1):3422. doi: 10.1038/s41598-019-39467-w.
The number of patients with dry eye disease (DED) is increasing, and DED has become an urgent public health problem. A comorbidity of mental disorders has been reported in DED patients. We hypothesized that physical and psychological stressors impair tear secretion. To examine the relationship between stress loading and decreased tear secretion, we established a stress-induced DED mouse model, which permitted us to address the underlying mechanism of pathogenesis and resilience. Enriched environment (EE) was an effective intervention to prevent and alleviate stress-induced decreased tear secretion. Because stress loading resulted in decreased brain-derived neurotrophic factor (BDNF) expression while EE resulted in increased expression, we focused on the role of BDNF in tear secretion. Using two distinct Bdnf gene knockdown mice, we evaluated whether BDNF was a deterministic factor in regulating tear secretion in healthy and stressed conditions. Bdnf knockdown mice showed decreased basal tear secretion and loss of stress tolerance by EE for tear secretion. These results suggest that BDNF expression is related to tear secretion and to the pathology of DED.
干眼症 (DED) 患者数量不断增加，DED 已成为一个紧迫的公共卫生问题。据报道，DED 患者存在精神障碍共病。我们假设身体和心理压力源会损害泪液分泌。为了研究应激负荷与泪液分泌减少之间的关系，我们建立了应激诱导的 DED 小鼠模型，这使我们能够研究发病机制和恢复力的潜在机制。丰富环境 (EE) 是预防和缓解应激诱导的泪液分泌减少的有效干预措施。因为应激负荷导致脑源性神经营养因子 (BDNF) 表达减少，而 EE 导致表达增加，所以我们专注于 BDNF 在泪液分泌中的作用。使用两种不同的 Bdnf 基因敲低小鼠，我们评估了 BDNF 是否是调节健康和应激状态下泪液分泌的决定性因素。Bdnf 敲低小鼠表现出基础泪液分泌减少和 EE 对泪液分泌的应激耐受性丧失。这些结果表明，BDNF 表达与泪液分泌以及 DED 的病理学有关。
