Journal article
Transplantation of iPSC-derived TM cells rescues glaucoma phenotypes in vivo
Proceedings of the National Academy of Sciences - PNAS, Vol.113(25), pp.E3492-E3500
06/21/2016
DOI: 10.1073/pnas.1604153113
PMCID: PMC4922164
PMID: 27274060
Abstract
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.
Details
- Title: Subtitle
- Transplantation of iPSC-derived TM cells rescues glaucoma phenotypes in vivo
- Creators
- Wei Zhu - 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 52242Oliver W Gramlich - Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, IA 52242Lauren Laboissonniere - Department of Genetics, Development, and Cell Biology, Iowa State University, Ames, IA 50011Ankur Jain - Department of Pediatrics, University of Iowa, Iowa City, IA 52242Val C Sheffield - 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 52242Jeffrey M Trimarchi - Department of Genetics, Development, and Cell Biology, Iowa State University, Ames, IA 50011Budd A Tucker - Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, IA 52242Markus H Kuehn - 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
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.113(25), pp.E3492-E3500
- DOI
- 10.1073/pnas.1604153113
- PMID
- 27274060
- PMCID
- PMC4922164
- NLM abbreviation
- Proc Natl Acad Sci U S A
- ISSN
- 0027-8424
- eISSN
- 1091-6490
- Publisher
- United States
- Grant note
- R01 NS083543 / NINDS NIH HHS R01 EY024259 / NEI NIH HHS I01 RX001163 / RRD VA
- Language
- English
- Date published
- 06/21/2016
- Academic Unit
- Stead Family Department of Pediatrics; The University of Iowa Institute for Vision Research; Iowa Neuroscience Institute; Medical Genetics and Genomics; Ophthalmology and Visual Sciences
- Record Identifier
- 9983979955802771
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