Extracellular matrix in the trabecular meshwork

Acott, Ted S.; Kelley, Mary J.

doi:10.1016/j.exer.2008.01.013

Cited by 408 publications

(459 citation statements)

References 189 publications

(335 reference statements)

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“…Here, we show the first experimental evidence that outflow pathway cell depletion in the approximate range observed in glaucoma does indeed compromise the function of the outflow pathway, which is maintaining IOP homeostasis [4,8]. Partial repopulation of the cell-depleted tissue with cultured TM cells is able to restore this key outflow pathway function, thereby further strengthening this evidence.…”

Section: Discussionsupporting

confidence: 56%

“…The TM has several zones of cells, and saponin was able to penetrate and kill cells in all zones down into the deepest zone, the juxtacanalicular region or JCT (Fig. 1D, 1E), which is the region thought to be responsible for IOP homeostasis [4,8,35]. Saponin treatment induced cell death although more live than dead cells still populated the TM, indicating that saponin's effect at this concentration was partial (Fig.…”

Section: Cellular Loss With Saponin Treatmentmentioning

confidence: 99%

“…Frontal sections (Fig. 5A, 5B) show that the transplanted cells were found throughout the TM, including the deepest JCT layer, which is thought to be the location of the outflow resistance [8,44]. The dashed lines around the Qdot-containing transplanted cells (Fig.…”

Section: Transplanted Tm-like Ipscs Integrated Into the Tm And Restormentioning

confidence: 99%

“…S1A). It is thought that these cells sense sustained IOP changes as mechanical stretching or distortion and adjust the extracellular matrix (ECM) to correct the outflow resistance [4][5][6][7][8][9]. Experimentally, IOP homeostasis is studied in ex vivo perfused anterior segment organ culture [4].…”

Section: Introductionmentioning

confidence: 99%

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Induced Pluripotent Stem Cells Restore Function in a Human Cell Loss Model of Open-Angle Glaucoma

DW¹,

X²

2016

J Clin Exp Ophthalmol

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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. STEM CELLS 2015;33:751-761

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Section: Discussionsupporting

confidence: 56%

Section: Cellular Loss With Saponin Treatmentmentioning

confidence: 99%

Section: Transplanted Tm-like Ipscs Integrated Into the Tm And Restormentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Induced Pluripotent Stem Cells Restore Function in a Human Cell Loss Model of Open-Angle Glaucoma

DW¹,

X²

2016

J Clin Exp Ophthalmol

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“…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 collagen beams and the accumulation of macromolecules have been observed that might increase outflow resistance (8,9). The stiffness of the TM in eyes with glaucoma is significantly increased compared with that of normal TM and it is likely that reduced elasticity has significant ramifications on IOP maintenance (10,11).…”

mentioning

confidence: 96%

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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Biomaterials for Regenerative Medicine Approaches for the Anterior Segment of the Eye

Williams

Lace

Kennedy

et al. 2018

Adv Healthcare Materials

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The role of biomaterials in tissue engineering and regenerative medicine strategies to treat vision loss associated with damage to tissues in the anterior segment of the eye has been studied for several years. This has mostly involved replacement and support for the cornea and conjunctiva. These are complex tissues with specific functional requirements for different parts of the tissue. Amniotic membrane (AM) is used in clinical practice to transplant autologous or allogenic cells to the corneal surface. Fibrin gels have also progressed to clinical use under specific conditions. Alternatives to AM such as collagen gels, other natural materials, for example keratin and silks, and synthetic polymers have received considerable attention in laboratory and animal studies. This experience is building a body of evidence to demonstrate the potential of tissue engineering and regenerative medicine in corneal and conjunctival reconstruction and can also lead to other applications in the anterior segment of the eye, for example, the trabecular meshwork. There is a real clinical need for new procedures to overcome vision loss but there are also opportunities for developments in ocular applications to lead to biomaterials innovations for use in other clinical areas.

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Extracellular matrix in the trabecular meshwork

Cited by 408 publications

References 189 publications

Induced Pluripotent Stem Cells Restore Function in a Human Cell Loss Model of Open-Angle Glaucoma

Induced Pluripotent Stem Cells Restore Function in a Human Cell Loss Model of Open-Angle Glaucoma

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

Biomaterials for Regenerative Medicine Approaches for the Anterior Segment of the Eye

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