Induced pluripotent stem cells restore function in a human cell loss model of open-angle glaucoma.
Normally, trabecular meshwork (TM) and Schlemm's canal inner wall endothelial cells within the aqueous humor outflow pathway maintain intraocular pressure within a narrow safe range. Elevation in intraocular pressure, because of the loss of homeostatic regulation by these outflow pathway cells, is the primary risk factor for vision loss due to glaucomatous optic neuropathy. A notable feature associated with glaucoma is outflow pathway cell loss. Using controlled cell loss in ex vivo perfused human outflow pathway organ culture, we developed compelling experimental evidence that this level of cell loss compromises intraocular pressure homeostatic function. This function was restored by repopulation of the model with fresh TM cells. We then differentiated induced pluripotent stem cells (iPSCs) and used them to repopulate this cell depletion model. These differentiated cells (TM-like iPSCs) became similar to TM cells in both morphology and expression patterns. When transplanted, they were able to fully restore intraocular pressure homeostatic function. This successful transplantation of TM-like iPSCs establishes the conceptual feasibility of using autologous stem cells to restore intraocular pressure regulatory function in open-angle glaucoma patients, providing a novel alternative treatment option.
Department of Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, USA; Department of Biochemistry & Molecular Biology, Oregon Health & Science University, Portland, Oregon, USA; Department of Biochemistry & Physiology, University of Jordan, Amman, Jordan.
Diala W
DW
Abu-Hassan
Xinbo
X
Li
Eileen I
EI
Ryan
Ted S
TS
Acott
Mary J
MJ
Kelley
D002454:Cell Differentiation / Q000502:physiology; D005902:Glaucoma, Open-Angle / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D048091:Guided Tissue Regeneration / Q000379:methods*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D033581:Stem Cell Transplantation / Q000379:methods*; D014182:Transplantation, Autologous
Autologous stem cell transplantation; Cell transplantation; Experimental models; Induced pluripotent stem cells; Somatic stem cells; Stem cell transplantation; Tissue regeneration; Transplantation