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Wei Zhu, Qiong Ding, Budd Tucker, Markus H Kuehn; Transplantation of iPSC-derived TM cells restores outflow facility in a mouse model of glaucoma. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3277.
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Dysfunction and loss of trabecular meshwork (TM) cells is associated with the pathology of primary open-angle glaucoma (POAG). The overall goal of this study is to determine if the TM in glaucomatous eyes can be functionally restored via transplantation of stem cell derived TM cells. Induced pluripotent stem cells (iPSCs) are an attractive choice for stem cell-based therapies due to the potential for autologous transplantation.
Mouse iPSCs were differentiated into a TM-like cell type (iPSC-TM) and cells with remaining SSEA-1 immunoreactivity were removed by magnetic separation. 50,000 iPSC-TM cells were injected into the anterior chamber of 4-month-old Tg-MYOCY437H (N=26 eyes). Controls included age-matched wild type littermates (N=14), Tg-MYOCY437H receiving vehicle-only (PBS) injections (N=18), or injections of fibroblasts (N=8). IOP and outflow facility were measured, and the distribution of transplanted cells was assessed using immunohistochemistry.
Within three weeks after transplantation of iPSC-TM the IOP in Tg-MYOCY437H declined from 14.95 mmHg to 13.08 mmHg (p=0.032), similar to that observed in wild-type mice (12.67 mmHg). In contrast, IOP of Tg-MYOCY437H having received either PBS or fibroblasts did not decrease (IOP 15.25 mmHg and 15.48 mmHg, respectively). The outflow facility in iPSC-TM mice recipients was 0.034 µl/min/mmHg, significantly higher than that in the PBS group (0.019 µl/min/mmHg, p<0.05). Immunohistochemical analysis revealed transplanted iPSC-TM in the TM of recipient mice, although off-target implantation was also commonly observed. Detrimental side effects such as tumor formation were observed in fewer than 8 % of iPSC-TM transplanted eyes.
Transplantation of mouse iPSC-TM cells enhances outflow of aqueous humor and decreases IOP in the transgenic MYOCY437H mouse model of glaucoma. These findings are encouraging and may point toward new approaches of stem cell-based therapy to restore TM function in POAG patients.
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