Identification of Adult Stem Cells in Schwalbe's Line Region of the Primate Eye

Braunger, Barbara M.; Ademoglu, Bahar; Koschade, Sebastian E.; Fuchshofer, Rudolf; Gabelt, B’Ann T.; Kiland, Julie A.; Hennes-Beann, Elizabeth A; Brunner, Kevin; Kaufman, Paul L.; Tamm, Ernst R.

doi:10.1167/iovs.14-14872

Cited by 55 publications

(33 citation statements)

References 53 publications

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“…The newly derived TM cells are derived from a population of progenitor cells located directly beneath the Schwalbe's line that are suspected to resemble stem cells (48). It is intriguing to speculate whether the endogenous TM cells re-entering the cell cycle following iPSC-TM transplantation belong to this particular TM cell subtype.…”

Section: Discussionmentioning

confidence: 99%

Transplantation of iPSC-derived TM cells rescues glaucoma phenotypes in vivo

Zhu

Gramlich

Laboissonniere

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

133

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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.G laucoma is one of the most common causes of irreversible vision loss and blindness worldwide; ∼60 million suffer from this disease, and of these, 7 million are blind (1). By definition all glaucoma involves some degree of vision loss, which is because of the death of retinal ganglion cells (RGC), as well as degeneration of the optic nerve head, the optic nerve, and the lateral geniculate nucleus (2, 3). Advanced age and elevated intraocular pressure (IOP) are the two most significant risk factors for the development of glaucoma. Elevated IOP is typically a result of disturbances in the balance of aqueous humor production and drainage. Aqueous humor is continuously synthesized within the eye and drained primarily through the trabecular meshwork (TM), a specialized structure located anterior to the root of the iris. Although occlusion of the aqueous humor outflow pathways can occur through several mechanisms, in the United States and other Western populations the most common form of glaucoma is primary open angle glaucoma (POAG), which manifests no gross abnormalities to the anterior portion of the eye.Randomized clinical trials have shown that reduction of IOP slows the onset and progression of glaucoma, even in patients without suspicious elevation of IOP (4, 5). Although there has been increasing awareness that factors other than elevated IOP contribute to glaucomatous damage, to date all treatments for glaucoma remain aimed at reducing IOP either through surgical or medical means, which has resulted in significant preservation of vision and increased quality of life for millions of glaucoma patients (6, 7).Although the TM in eyes with POAG appears relatively normal at a gross morphological level, a number of more subtle changes influencing the mechanical properties of the TM collage...

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Section: Discussionmentioning

confidence: 99%

Transplantation of iPSC-derived TM cells rescues glaucoma phenotypes in vivo

Zhu

Gramlich

Laboissonniere

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

133

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“…Braunger et al 50 identified stem cells in the anterior chamber angle of the monkey eyes by detecting BrdU longterm retention. They treated 4 monkeys with BrdU for 4 weeks and found that the number of BrdU-positive cells was higher at Schwalbe's line covering the peripheral end of Descemet's membrane than in regions of JCT, TM, and scleral spur.…”

Section: Label-retaining Assaysmentioning

confidence: 99%

Stem Cells in the Trabecular Meshwork for Regulating Intraocular Pressure

Yun

Zhou

Wills

et al. 2016

Journal of Ocular Pharmacology and Therapeutics

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Intraocular pressure (IOP) is still the main treatment target for glaucoma. Outflow resistance mainly exists at the trabecular meshwork (TM) outflow pathway, which is responsible for IOP regulation. Changes of TM cellularity and TM extracellular matrix turnover may play important roles in IOP regulation. In this article, we review basic anatomy and physiology of the outflow pathway and TM stem cell characteristics regarding the location, isolation, identification and function. TM stem cells are localized at the insert region of the TM and are label-retaining in vivo. They can be isolated by side-population cell sorting, cloning culture, or sphere culture. TM stem cells are multipotent with the ability to home to the TM region and differentiate into TM cells in vivo. Other stem cell types, such as adipose-derived stem cells, mesenchymal stem cells and induced pluripotent stem cells have been discovered for TM cell differentiation and TM regeneration. We also review glaucomatous animal models, which are suitable to study stem cell-based therapies for TM regeneration.

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“…Adult stem cells have also been identified in the region of Schwalbe's line adjacent to Descemet's membrane in primate eyes. These cells retained BrdU and displayed OCT 4 immunoreactivity [57]. A similar region was observed in human TM by Acott et alwho found 4-fold replication of cells in the anterior TM adjacent to Schwalbe's line after treatment with laser trabeculoplasty [58].…”

Section: Introductionmentioning

confidence: 73%

Recent Developments in Understanding the Role of Aqueous Humor Outflow in Normal and Primary Open Angle Glaucoma

Hann

Fautsch

2015

Curr Ophthalmol Rep

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Primary open angle glaucoma (POAG) is the second leading cause of blindness in the world's rapidly aging population. POAG is characterized by progressive degeneration of neural structures in the posterior segment, often associated with a concomitant elevation of intraocular pressure. Changes in IOP are believed to be caused by a disruption in the normal outflow of aqueous humor. This article reviews recent research associated with normal and POAG aqueous humor outflow. Novel findings elucidating biochemical and pathological changes in the ocular tissues affected in POAG are presented. Stem cell research, identification of lymphatic markers, and increased use of mouse models give researchers exciting new tools to understand aqueous humor outflow, changes associated with POAG and identify underlying causes of the disease.

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Identification of Adult Stem Cells in Schwalbe's Line Region of the Primate Eye

Abstract: We provide evidence for a niche in the Schwalbe's line region harboring cells with long-term BrdU retention and OCT4 immunoreactivity. The cells likely constitute a population of adult stem cells with the capability to compensate for the loss of TM and/or corneal endothelial cells.

Cited by 55 publications

References 53 publications

Transplantation of iPSC-derived TM cells rescues glaucoma phenotypes in vivo

Transplantation of iPSC-derived TM cells rescues glaucoma phenotypes in vivo

Stem Cells in the Trabecular Meshwork for Regulating Intraocular Pressure

Recent Developments in Understanding the Role of Aqueous Humor Outflow in Normal and Primary Open Angle Glaucoma

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