Grupo de Inmunodeficiencias Primarias, Facultad de Medicina, Universidad de Antioquia, UdeA, Medellín 050010, Colombia.
Ocular Surface Center, Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, TX 77030, USA.
Int J Mol Sci. 2020 Nov 24;21(23):8890. doi: 10.3390/ijms21238890.
Dry eye disease (DED), one of the most prevalent conditions among the elderly, is a chronic inflammatory disorder that disrupts tear film stability and causes ocular surface damage. Aged C57BL/6J mice spontaneously develop DED. Rapamycin is a potent immunosuppressant that prolongs the lifespan of several species. Here, we compared the effects of daily instillation of eyedrops containing rapamycin or empty micelles for three months on the aged mice. Tear cytokine/chemokine profile showed a pronounced increase in vascular endothelial cell growth factor-A (VEGF-A) and a trend towards decreased concentration of Interferon gamma (IFN)-γ in rapamycin-treated groups. A significant decrease in inflammatory markers in the lacrimal gland was also evident (, , and ); this was accompanied by slightly diminished () transcripts. In the lacrimal gland and draining lymph nodes, we also observed a significant increase in the CD45CD4Foxp3 cells in the rapamycin-treated mice. More importantly, rapamycin eyedrops increased conjunctival goblet cell density and area compared to the empty micelles. Taken together, evidence from these studies indicates that topical rapamycin has therapeutic efficacy for age-associated ocular surface inflammation and goblet cell loss and opens the venue for new investigations on its role in the aging process of the eye.
干眼症（DED）是老年人中最常见的疾病之一，是一种慢性炎症性疾病，破坏泪膜稳定性并导致眼表面损伤。老年 C57BL/6J 小鼠自发发生 DED。雷帕霉素是一种强效的免疫抑制剂，可延长几种物种的寿命。在这里，我们比较了三个月内每天滴眼含有雷帕霉素或空胶束对老年小鼠的影响。泪液细胞因子/趋化因子谱显示血管内皮细胞生长因子-A（VEGF-A）明显增加，干扰素γ（IFN-γ）浓度呈下降趋势。在泪腺中也明显减少了炎症标志物（、、和）；这伴随着略微减少的 () 转录物。在泪腺和引流淋巴结中，我们还观察到雷帕霉素处理的小鼠中 CD45CD4Foxp3 细胞显著增加。更重要的是，雷帕霉素滴眼剂与空胶束相比，增加了结膜杯状细胞的密度和面积。总之，这些研究的证据表明，局部雷帕霉素对与年龄相关的眼表面炎症和杯状细胞丢失具有治疗效果，并为其在眼睛衰老过程中的作用的新研究开辟了途径。
