Stem Cells in the Trabecular Meshwork for Regulating Intraocular Pressure

Yun, Hongmin; Zhou, Yi; Wills, Andrew C.; Du, Yiqin

doi:10.1089/jop.2016.0005

Cited by 52 publications

(47 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The candidate TM marker AQP1 was preferentially expressed in these non-filtering TM cells, consistent with the observation that deletion of AQP1 in mice did not affect outflow facility (Figure 3J) (Zhang et al, 2002). Although it has been suggested that Schwalbe's line contains TM precursors (Kelley et al, 2009), we detected no DE genes suggestive of "stemness" (Yun et al, 2016) in this cluster; if present, they may have been too rare to be detected.…”

Section: Introductionsupporting

confidence: 88%

Cell Atlas of Aqueous Humor Outflow Pathways in Eyes of Humans and Four Model Species Provides Insights into Glaucoma Pathogenesis

Zyl

Yan

McAdams

et al. 2020

Preprint

View full text Add to dashboard Cite

ABSTRACTIncreased intraocular pressure (IOP) represents a major risk factor for glaucoma, a prevalent eye disease characterized by death of retinal ganglion cells that carry information from the eye to the brain; lowering IOP is the only proven treatment strategy to delay disease progression. The main determinant of IOP is the equilibrium between production and drainage of aqueous humor, with compromised drainage generally viewed as the primary contributor to dangerous IOP elevations. Drainage occurs through two pathways in the anterior segment of the eye, called conventional and uveoscleral. To gain insights into the cell types that comprise these pathways, we used high-throughput single cell RNA sequencing (scRNA-seq). From ∼24,000 single cell transcriptomes, we identified 19 cell types with molecular markers for each and used histological methods to localize each type. We then performed similar analyses on four organisms used for experimental studies of IOP dynamics and glaucoma: cynomolgus macaque (Macaca fascicularis), rhesus macaque (Macaca mulatta), pig (Sus scrofa) and mouse (Mus musculus). Many human cell types had counterparts in these models, but differences in cell types and gene expression were evident. Finally, we identified the cell types that express genes implicated in glaucoma in all five species. Together, our results provide foundations for investigating the pathogenesis of glaucoma, and for using model systems to assess mechanisms and potential interventions.

show abstract

Section: Introductionsupporting

confidence: 88%

Cell Atlas of Aqueous Humor Outflow Pathways in Eyes of Humans and Four Model Species Provides Insights into Glaucoma Pathogenesis

Zyl

Yan

McAdams

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…It has been reported that there are tissue‐specific stem cells in the TM 26‐30 . Several groups have successfully isolated and characterized human TM stem cells 31‐33 .…”

Section: Introductionmentioning

confidence: 99%

Adipose‐derived stem cells integrate into trabecular meshwork with glaucoma treatment potential

et al. 2020

Self Cite

View full text Add to dashboard Cite

The trabecular meshwork (TM) is an ocular tissue that maintains intraocular pressure (IOP) within a physiologic range. Glaucoma patients have reduced TM cellularity and, frequently, elevated IOP. To establish a stem cell-based approach to restoring TM function and normalizing IOP, human adipose-derived stem cells (ADSCs) were induced to differentiate to TM cells in vitro. These ADSC-TM cells displayed a TM cell-like genotypic profile, became phagocytic, and responded to dexamethasone stimulation, characteristic of TM cells. After transplantation into naive mouse eyes, ADSCs and ADSC-TM cells integrated into the TM tissue, expressed TM cell markers, and maintained normal IOP, outflow facility, and extracellular matrix. Cell migration and affinity results indicated that the chemokine pair CXCR4/SDF1 may play an important role in ADSC-TM cell homing. Our study demonstrates the possibility of applying autologous or allogeneic ADSCs and ADSC-TM cells as a potential treatment to restore TM structure and function in glaucoma. K E Y W O R D Sadipose stem cells; differentiation, homing, integration, trabecular meshwork | 7161 ZHOU et al.

show abstract

“…Recent studies suggested not only low TM cellularity (Alvarado, Murphy & Juster, 1984;Baleriola et al, 2008), but also TM cytoskeleton and phagocytosis changes in primary open angle glaucoma (Clark et al, 1995;Fatma et al, 2009;Izzotti et al, 2010;Saccà, Pulliero & Izzotti, 2015;Peters et al, 2015;Micera et al, 2016). Repopulating diseased TM with fresh, functional TM cells has been shown to restore homeostasis of normal outflow and thus might represent a novel therapeutic breakthrough (Du et al, 2013;Abu-Hassan et al, 2015;Yun et al, 2016;Zhu et al, 2016). …”

Section: Introductionmentioning

confidence: 99%

Freeze-thaw decellularization of the trabecular meshwork in an ex vivo eye perfusion model

Dang

Waxman

Wang

et al. 2017

Preprint

View full text Add to dashboard Cite

Freeze-thaw decellularization of the trabecular meshwork in an ex vivo eye perfusion model Materials and Methods:We obtained 24 porcine eyes from a local abattoir, dissected and mounted them in an anterior segment perfusion and pressure transduction system within two hours of sacrifice. After they stabilized for 72 hours, eight eyes each were assigned to freeze-thaw (F) ablation (-80°C×2), to 0.02% saponin (S) treatment, or the control group (C), respectively. The trabecular meshwork was transduced with an eGFP expressing feline immunodeficiency viral (FIV) vector and tracked via fluorescent microscopy to confirm ablation. Following treatment, the eyes were perfused with standard tissue culture medium for 180 hours. We assessed histological changes by hematoxylin and eosin staining. TM cell viability was evaluated with a calcein AM/propidium iodide (PI) assay. We measured IOP and modeled it with a linear mixed effects model using a B-spline function of time with 5 degrees of freedom.Results: F and S experienced a similar IOP reduction by 30% from baseline (P =0.64). IOP reduction of about 30% occurred in F within 24 hours and in S within 48 hours. Live visualization of eGFP demonstrated that F conferred a complete ablation of all TM cells and only a partial ablation in S. Histological analysis confirmed that no TM cells survived in F while the extracellular matrix remained. The viability assay showed very low PI and no calcein staining in F in contrast to numerous PI-labeled dead TM cells and calcein-labeled viable TM cells in S. Conclusion:We developed a rapid TM ablation method that uses cyclic freezing that is free of biological or chemical agents and able to produce a decellularized TM scaffold with preserved TM extracellular matrix in an organotypic perfusion culture.

show abstract

Stem Cells in the Trabecular Meshwork for Regulating Intraocular Pressure

Cited by 52 publications

References 62 publications

Cell Atlas of Aqueous Humor Outflow Pathways in Eyes of Humans and Four Model Species Provides Insights into Glaucoma Pathogenesis

Cell Atlas of Aqueous Humor Outflow Pathways in Eyes of Humans and Four Model Species Provides Insights into Glaucoma Pathogenesis

Adipose‐derived stem cells integrate into trabecular meshwork with glaucoma treatment potential

Freeze-thaw decellularization of the trabecular meshwork in an ex vivo eye perfusion model

Contact Info

Product

Resources

About