Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, 15261, USA.
Department of Chemical Engineering, University of Pittsburgh, Pittsburgh, PA, 15216, USA.
Sci Rep. 2017 Dec 13;7(1):17527. doi: 10.1038/s41598-017-17869-y.
Dry eye disease (DED) is a highly prevalent, ocular disorder characterized by an abnormal tear film and ocular surface. Recent experimental data has suggested that the underlying pathology of DED involves inflammation of the lacrimal functional unit (LFU), comprising the cornea, conjunctiva, lacrimal gland and interconnecting innervation. This inflammation of the LFU ultimately results in tissue deterioration and the symptoms of DED. Moreover, an increase of pathogenic lymphocyte infiltration and the secretion of pro-inflammatory cytokines are involved in the propagation of DED-associated inflammation. Studies have demonstrated that the adoptive transfer of regulatory T cells (Tregs) can mediate the inflammation caused by pathogenic lymphocytes. Thus, as an approach to treating the inflammation associated with DED, we hypothesized that it was possible to enrich the body's own endogenous Tregs by locally delivering a specific combination of Treg inducing factors through degradable polymer microspheres (TRI microspheres; TGF-β1, Rapamycin (Rapa), and IL-2). This local controlled release system is capable of shifting the balance of Treg/T effectors and, in turn, preventing key signs of dry eye disease such as aqueous tear secretion, conjunctival goblet cells, epithelial corneal integrity, and reduce the pro-inflammatory cytokine milieu in the tissue.
干眼症（DED）是一种高度普遍的眼疾，其特征为异常的泪膜和眼表面。最近的实验数据表明，DED 的潜在病理学涉及泪液功能单位（LFU）的炎症，包括角膜、结膜、泪腺和相互连接的神经支配。LFU 的这种炎症最终导致组织恶化和 DED 症状。此外，致病性淋巴细胞浸润的增加和促炎细胞因子的分泌参与了 DED 相关炎症的传播。研究表明，调节性 T 细胞（Tregs）的过继转移可以介导致病性淋巴细胞引起的炎症。因此，作为治疗与 DED 相关炎症的一种方法，我们假设通过可降解聚合物微球（TRI 微球；TGF-β1、雷帕霉素（Rapa）和 IL-2）局部递送来诱导 Treg 的特定组合，可以使体内自身的内源性 Tregs 丰富。这种局部控制释放系统能够改变 Treg/T 效应物的平衡，从而防止干眼症的关键迹象，如水性泪液分泌、结膜杯状细胞、上皮角膜完整性，并减少组织中的促炎细胞因子环境。
