Department of Ophthalmology, University of Pittsburgh, Pittsburgh, PA, USA.
Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, China.
FASEB J. 2020 May;34(5):7160-7177. doi: 10.1096/fj.201902326R. Epub 2020 Apr 7.
The trabecular meshwork (TM) is an ocular tissue that maintains intraocular pressure (IOP) within a physiologic range. Glaucoma patients have reduced TM cellularity and, frequently, elevated IOP. To establish a stem cell-based approach to restoring TM function and normalizing IOP, human adipose-derived stem cells (ADSCs) were induced to differentiate to TM cells in vitro. These ADSC-TM cells displayed a TM cell-like genotypic profile, became phagocytic, and responded to dexamethasone stimulation, characteristic of TM cells. After transplantation into naive mouse eyes, ADSCs and ADSC-TM cells integrated into the TM tissue, expressed TM cell markers, and maintained normal IOP, outflow facility, and extracellular matrix. Cell migration and affinity results indicated that the chemokine pair CXCR4/SDF1 may play an important role in ADSC-TM cell homing. Our study demonstrates the possibility of applying autologous or allogeneic ADSCs and ADSC-TM cells as a potential treatment to restore TM structure and function in glaucoma.
小梁网（TM）是一种维持眼内压（IOP）在生理范围内的眼组织。青光眼患者的 TM 细胞减少，并且经常伴有 IOP 升高。为了建立一种基于干细胞的方法来恢复 TM 功能并使 IOP 正常化，我们诱导人脂肪来源的干细胞（ADSCs）在体外分化为 TM 细胞。这些 ADSC-TM 细胞表现出 TM 细胞样的基因型特征，具有吞噬作用，并对 TM 细胞的特征性物质地塞米松刺激产生反应。将 ADSC 和 ADSC-TM 细胞移植到未成熟的小鼠眼中后，它们整合到 TM 组织中，表达 TM 细胞标志物，并维持正常的 IOP、流出物功能和细胞外基质。细胞迁移和亲和性结果表明，趋化因子对 CXCR4/SDF1 可能在 ADSC-TM 细胞归巢中发挥重要作用。我们的研究表明，应用自体或同种异体 ADSC 和 ADSC-TM 细胞作为恢复青光眼 TM 结构和功能的潜在治疗方法是可行的。
