Department of Pharmacology, Qingdao University, Qingdao, P.R. China.
Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, IA, 52242, USA.
Sci Rep. 2020 Feb 19;10(1):2905. doi: 10.1038/s41598-020-59941-0.
The trabecular meshwork's (TM) physiological role is to maintain normal intraocular pressure by regulating aqueous humor outflow. With age, and particularly in eyes with primary open angle glaucoma, the number of cells residing within the TM is markedly decreased and the function of the tissue is compromised. Here we evaluate if transplantation of induced pluripotent stem cell derived TM like cells (iPSC-TM) restores TM cellularity and function in human eyes obtained from older human donors. Human iPSC were differentiated into iPSC-TM and compared to primary TM cells by RNAseq. iPSC-TM were then injected into the anterior segments of human eyes maintained in perfusion culture. Seven and 14 days eyes after injection eyes that received iPSC-TM contained significantly more cells in the TM. Fewer than 1% of all cells appeared to be iPSC-TM, but significantly more cells in these eyes were immunopositive for Ki 67 and incorporated BrdU. Our study demonstrates that transplantation iPSC-TM stimulates proliferation of endogenous TM cells in perfusion cultured human eyes from aged donors. These data, in concert with our previous findings in animal models, suggest that functional regeneration of the TM may be possible in human eyes with primary open angle glaucoma.
小梁网（TM）的生理作用是通过调节房水流出来维持正常眼压。随着年龄的增长，特别是在原发性开角型青光眼的眼中，TM 内的细胞数量明显减少，组织功能受损。在这里，我们评估诱导多能干细胞衍生的 TM 样细胞（iPSC-TM）移植是否能恢复从老年供体获得的人眼中的 TM 细胞数量和功能。将人诱导多能干细胞分化为 iPSC-TM，并通过 RNAseq 与原代 TM 细胞进行比较。然后将 iPSC-TM 注射到保持在灌注培养中的人眼前段。注射后 7 天和 14 天，接受 iPSC-TM 的眼睛 TM 中的细胞数量明显增加。尽管只有不到 1%的细胞似乎是 iPSC-TM，但这些眼睛中有更多的细胞对 Ki 67 免疫阳性，并掺入 BrdU。我们的研究表明，在灌注培养的来自老年供体的人眼中，iPSC-TM 移植可刺激内源性 TM 细胞的增殖。这些数据与我们以前在动物模型中的发现一致，表明在原发性开角型青光眼的人眼中，TM 的功能再生可能是可行的。
