Journal article
Restoration of Aqueous Humor Outflow Following Transplantation of iPSC-Derived Trabecular Meshwork Cells in a Transgenic Mouse Model of Glaucoma
Investigative ophthalmology & visual science, Vol.58(4), pp.2054-2062
04/01/2017
DOI: 10.1167/iovs.16-20672
PMCID: PMC6108236
PMID: 28384726
Abstract
Primary open-angle glaucoma (POAG) is particularly common in older individuals and associated with pathologic degeneration of the trabecular meshwork (TM). We have shown previously that transplantation of induced pluripotent stem cell (iPSC) derived TM cells restores aqueous humor dynamics in young transgenic mice expressing a pathogenic form of human myocilin (Tg-MYOCY437H). This study was designed to determine if this approach is feasible in older mice with more pronounced TM dysfunction. Mouse iPSC were differentiated toward a TM cell phenotype (iPSC-TM) and injected into the anterior chamber of 6-month-old Tg-MYOCY437H or control mice. IOP and aqueous humor outflow facility were recorded for up to 3 months. Transmission electron microscopy, Western blot, and immunohistochemistry were performed to analyze TM morphology, quantify endoplasmic reticulum (ER) stress, and assess TM cellularity. A 12 weeks after transplantation, IOP in iPSC-TM recipients was statistically lower and outflow facility was significantly improved compared to untreated controls. The number of endogenous TM cells increased significantly in iPSC-TM recipients along with the appearance of TM cells immmunopositive for a marker of cellular division. Morphologically, transplantation of iPSC-TM preserves ER structure 12 weeks after transplantation. However, myocilin and calnexin expression levels remain elevated in transplanted eyes of these 9-month-old Tg-MYOCY437H mice, indicating that ER stress persists within the TM. Transplantation of iPSC-TM can restore IOP and outflow facility in aged Tg-MYOCY437H mice. This type of stem cell-based therapy is a promising possibility for restoration of IOP control in some glaucoma patients.
Details
- Title: Subtitle
- Restoration of Aqueous Humor Outflow Following Transplantation of iPSC-Derived Trabecular Meshwork Cells in a Transgenic Mouse Model of Glaucoma
- Creators
- Wei Zhu - University of IowaAnkur Jain - Department of Pediatrics, University of Iowa, Iowa City, Iowa, United StatesOliver W Gramlich - University of IowaBudd A Tucker - University of IowaVal C Sheffield - University of IowaMarkus H Kuehn - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Investigative ophthalmology & visual science, Vol.58(4), pp.2054-2062
- DOI
- 10.1167/iovs.16-20672
- PMID
- 28384726
- PMCID
- PMC6108236
- NLM abbreviation
- Invest Ophthalmol Vis Sci
- ISSN
- 0146-0404
- eISSN
- 1552-5783
- Publisher
- United States
- Grant note
- I01 RX001163 / RRD VA P30 EY025580 / NEI NIH HHS
- Language
- English
- Date published
- 04/01/2017
- 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
- 9983979965302771
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