Transplantation of iPSC-derived TM cells rescues glaucoma phenotypes in vivo.
Glaucoma is a common cause of vision loss or blindness and reduction of intraocular pressure (IOP) has been proven beneficial in a large fraction of glaucoma patients. The IOP is maintained by the trabecular meshwork (TM) and the elevation of IOP in open-angle glaucoma is associated with dysfunction and loss of the postmitotic cells residing within this tissue. To determine if IOP control can be maintained by replacing lost TM cells, we transplanted TM-like cells derived from induced pluripotent stem cells into the anterior chamber of a transgenic mouse model of glaucoma. Transplantation led to significantly reduced IOP and improved aqueous humor outflow facility, which was sustained for at least 9 wk. The ability to maintain normal IOP engendered survival of retinal ganglion cells, whose loss is ultimately the cause for reduced vision in glaucoma. In vivo and in vitro analyses demonstrated higher TM cellularity in treated mice compared with littermate controls and indicated that this increase is primarily because of a proliferative response of endogenous TM cells. Thus, our study provides in vivo demonstration that regeneration of the glaucomatous TM is possible and points toward novel approaches in the treatment of this disease.
Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, IA 52242; Center for the Prevention and Treatment of Visual Loss, Iowa City Veterans Affairs Medical Center, Iowa City, IA 52242;
Wei
W
Zhu
Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, IA 52242;
Oliver W
OW
Gramlich
Department of Genetics, Development, and Cell Biology, Iowa State University, Ames, IA 50011;
Lauren
L
Laboissonniere
Department of Pediatrics, University of Iowa, Iowa City, IA 52242;
Ankur
A
Jain
Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, IA 52242; Department of Pediatrics, University of Iowa, Iowa City, IA 52242; Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City, IA 52242.
Val C
VC
Sheffield
Department of Genetics, Development, and Cell Biology, Iowa State University, Ames, IA 50011;
Jeffrey M
JM
Trimarchi
Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, IA 52242;
Budd A
BA
Tucker
Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, IA 52242; Center for the Prevention and Treatment of Visual Loss, Iowa City Veterans Affairs Medical Center, Iowa City, IA 52242; markus-kuehn@uiowa.edu.
Markus H
MH
Kuehn
D000818:Animals; D003598:Cytoskeletal Proteins / Q000235:genetics; D004195:Disease Models, Animal; D005136:Eye Proteins / Q000235:genetics; D005901:Glaucoma / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D007429:Intraocular Pressure; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D033581:Stem Cell Transplantation; D014129:Trabecular Meshwork / Q000473:pathology*; D000099179:Myocilin
D003598:Cytoskeletal Proteins; D005136:Eye Proteins; D006023:Glycoproteins; D000099179:Myocilin
glaucoma; iPSC; myocilin; trabecular meshwork