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Abstract #120869 Published in IGR 25-1
Magnetically Steered Cell Therapy For Functional Restoration Of Intraocular Pressure Control In Open-Angle Glaucoma
Fard MRB; Chan J; Read AT; Li G; Cheng L; Safa BN; Siadat SM; Siadat SM; Jhunjhunwala A; Grossniklaus HE; Emelianov SY; Stamer WD; Kuehn MH; Ethier CRbioRxiv : the preprint server for biology 2024; 0:
Trabecular meshwork (TM) cell therapy has been proposed as a next-generation treatment for elevated intraocular pressure (IOP) in glaucoma, the most common cause of irreversible blindness. Using a magnetic cell steering technique with excellent efficiency and tissue-specific targeting, we delivered two types of cells into a mouse model of glaucoma: either human adipose-derived mesenchymal stem cells (hAMSCs) or induced pluripotent cell derivatives (iPSC-TM cells). We observed a 4.5 [3.1, 6.0] mmHg or 27% reduction in intraocular pressure (IOP) for nine months after a single dose of only 1500 magnetically-steered hAMSCs, associated with restoration of function to the conventional outflow pathway, as judged by increased outflow facility and TM cellularity. iPSC-TM cells were also effective, but less so, showing only a 1.9 [0.4, 3.3] mmHg or 13% IOP reduction and increased risk of tumorigenicity. In both cases, injected cells remained detectable in the iridocorneal angle three weeks post-transplantation. Based on the locations of the delivered cells, the mechanism of IOP lowering is most likely paracrine signaling. We conclude that magnetically-steered hAMSC cell therapy has potential for long-term treatment of ocular hypertension in glaucoma. ONE SENTENCE SUMMARY: A novel magnetic cell therapy provided effective intraocular pressure control in a mouse model of glaucoma, motivating future translational studies.
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