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Wei Zhu, Emmanuel S Buys, Markus H Kuehn; Transplantation of iPSC-TM decreases IOP in aged sGC-/- mice. Invest. Ophthalmol. Vis. Sci. 2017;58(8):3774. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
We previously investigated the therapeutic role of induced pluripotent stem cells derived trabecular meshwork cells (iPSC-TM) in glaucomatous myocilinY437H transgenic mice. The goal of this study was to test the effect of iPSC-TM in a distinct glaucomatous mouse model caused by the deficiency of soluble guanylate cyclase (sGC) and to determine the therapeutic potential of iPSC-TM transplantation in aged mice.
TM cellularity in 14-mon-old sGC-/- mice (n=6) and age matched WT mice (n=8) was assessed by immunohistochemistry (IHC). iPSC-TM were purified and characterized by IHC. 50,000 iPSC-TM were injected into the anterior chamber of 12 month-old sGC-/- mice (n=15). Age matched PBS recipients (n=7) and wild type mice (n=8) were used as the vehicle and positive control. IOP was tracked by rebound tonometry. TM cellularity after transplantation was analyzed using morphometric approaches.
TM cellularity was lower in 14-month-old sGC-/- mice than in age matched WT mice (17.78 and 24.97 TM cells/section, respectivelyP=0.046). Four weeks after injection of iPSC-TM or an equal volume PBS (vehicle control) into the anterior chamber of 12-month-old sGC-/- mice, IOP was still similar in iPSC-TM recipients and vehicle control mice (13.98 mmHg and 14.42 mmHg, respectively P=0.60) and higher than in age-matched WT mice (11.60 mmHg). However, seven weeks after treatment, IOP was lower in iPSC-TM recipients than in vehicle control mice (12.71 mmHg and 13.78 mmHg, respectively, P=0.046). The IOP measured in transplanted mice is similar to that of WT mice (12.97 mmHg). Morphometric analysis revealed higher TM cellularity in iPSC-TM recipients than in vehicle control mice (22.34 and 16.42 TM cells/anterior segment, respectively, P=0.0059). TM cellularity was similar in iPSC-TM recipients and WT mice (24.9 TM cells/anterior segment).
Restoration of the TM via iPSC-TM transplantation is an efficient approach to treat TM degeneration resulting from a variety of etiologies. Furthermore, transplantation improves IOP and TM cellularity even in very old individuals. These are encouraging findings indicating the therapeutic potential of regenerating the TM in the majority of POAG cases.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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