Circumferential trabecular meshwork cell density in the human eye

Kuehn, Markus H.; Vranka, Janice A.; Wadkins, David; Jackson, Thomas E.; Cheng, Lin; Ledolter, Johannes

doi:10.1016/j.exer.2021.108494

Cited by 8 publications

(5 citation statements)

References 29 publications

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“…The results of the in vivo TM measurements were similar to those of our previous study, 10 showing that the TM thickness of eyes with POAG was significantly smaller than that of healthy eyes. Increased IOP 22 and TM atrophy (reduction of cellularity 23 and loss of TM cells 24 ) can cause a decrease in TM thickness. Regarding SC, both ultrasound biomicroscopy and OCT images showed a reduction in SC dimension in eyes with POAG 10,25 .…”

Section: Discussionmentioning

confidence: 99%

Changes to Outflow Structures After Pilocarpine in Primary Open Angle Glaucoma Compared With Healthy Individuals Using Optical Coherence Tomography

Chen

Deng

et al. 2022

Journal of Glaucoma

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Précis: Lower response of aqueous outflow pathway structures after pilocarpine could be observed in primary open angle glaucoma (POAG) patients, which is likely to be helpful for understanding intraocular pressure (IOP) evaluation in glaucoma. Purpose: To evaluate the morphologic changes in the trabecular meshwork (TM), Schlemm canal (SC), scleral spur (SS), and ciliary muscle after miosis in patients with POAG and healthy individuals. Methods: A total of 30 patients with POAG and 26 healthy controls were recruited. All participants underwent complete ophthalmologic examinations, including IOP and swept-source optical coherence tomography (OCT), before and 1 hour after the local administration of pilocarpine (2%). OCT measurements included TM thickness and width, SC diameter and area, SS length, ciliary muscle thickness, and ciliary muscle angle (CMA). Results: Pilocarpine administration induced a decline in IOP (15.6±2.3–14.6±2.2 mm Hg), decrease in nasal SS length (196.31±47.75–171.52±33.93 μm), decrease in TM thickness (90.18±16.43–83.02±13.74 μm), and increase in SC diameter (134.84±32.28–162.08±48.67 μm) and SC area (3851.37±1455.07–4801.39±1762.37 μm2 ) among healthy controls. In contrast, no significant changes in IOP and OCT measurements were found in patients with POAG. At baseline, CMA was independently correlated with IOP in normal eyes. After miosis, the change in TM thickness was independently correlated with changes in IOP in normal eyes; in eyes with POAG, changes in SS length and CMA were independently associated with changes in IOP. Conclusions: Topical pilocarpine-induced morphologic changes to outflow pathway structures in healthy individuals without significant changes in POAG. The lower response observed in patients with glaucoma may be relevant to understanding IOP changes.

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Section: Discussionmentioning

confidence: 99%

Changes to Outflow Structures After Pilocarpine in Primary Open Angle Glaucoma Compared With Healthy Individuals Using Optical Coherence Tomography

Chen

Deng

et al. 2022

Journal of Glaucoma

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“…The TM is a dynamic, multilayer, filter-like structure that responds to environmental signals like mechanical strain and shear forces with cytoskeletal and extracellular matrix (ECM) changes to maintain a normal IOP [9][10][11][12][13]. In glaucoma, the TM is characterized by senescence [14,15], increased TM stiffness [16], and reduced cellularity [17].…”

Section: Key Messagesmentioning

confidence: 99%

Tissue-engineered anterior segment eye cultures demonstrate hallmarks of conventional organ culture

Waxman

Strzalkowska

Wang

et al. 2022

Graefes Arch Clin Exp Ophthalmol

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Background Glaucoma is a blinding disease largely caused by dysregulation of outflow through the trabecular meshwork (TM), resulting in elevated intraocular pressure (IOP). We hypothesized that transplanting TM cells into a decellularized, tissue-engineered anterior segment eye culture could restore the outflow structure and function. Methods Porcine eyes were decellularized with freeze–thaw cycles and perfusion of surfactant. We seeded control scaffolds with CrFK cells transduced with lentiviral vectors to stably express eGFP and compared them to scaffolds seeded with primary TM cells as well as to normal, unaltered eyes. We tracked the repopulation behavior, performed IOP maintenance challenges, and analyzed the histology. Results Transplanted cells localized to the TM and progressively infiltrated the extracellular matrix, reaching a distribution comparable to normal, unaltered eyes. After a perfusion rate challenge to mimic a glaucomatous pressure elevation, transplanted and normal eyes reestablished a normal intraocular pressure (transplanted = 16.5 ± 0.9 mmHg, normal = 16.9 ± 0.9). However, eyes reseeded with eGFP-expressing CrFK cells could not regulate IOP, remaining high and unstable (27.0 ± 6.2 mmHg) instead. Conclusion Tissue-engineered anterior segment scaffolds can serve as readily available, scalable ocular perfusion cultures. This could reduce dependency on scarce donor globes in outflow research and may allow engineering perfusion cultures with specific geno- and phenotypes.

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“…Subsequent studies using TM cells isolated from these high and low outflow regions have also identified differences in the ECM proteins expressed by these cells but only after a prolonged time in culture [33]. Studies have also shown that variations in TM cellularity in high and low outflow regions do exist, but these differences did not appear to be correlated with segmental outflow [34]. Although the molecular differences identified in these segmental areas are likely to be correlated with differential outflow facility across different areas of the TM circumference [35], the molecular mechanism(s) that control normal aqueous humor outflow are still poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Digital spatial profiling of segmental outflow regions in trabecular meshwork reveals a role for ADAM15

Faralli,

Filla,

Yang

et al. 2024

PLoS ONE

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In this study we used a spatial transcriptomics approach to identify genes specifically associated with either high or low outflow regions in the trabecular meshwork (TM) that could potentially affect aqueous humor outflow in vivo. High and low outflow regions were identified and isolated from organ cultured human anterior segments perfused with fluorescently-labeled 200 nm FluoSpheres. The NanoString GeoMx Digital Spatial Profiler (DSP) platform was then used to identified genes in the paraffin embedded tissue sections from within those regions. These transcriptome analyses revealed that 16 genes were statistically upregulated in high outflow regions and 57 genes were statistically downregulated in high outflow regions when compared to low outflow regions. Gene ontology enrichment analysis indicated that the top three biological categories of these differentially expressed genes were ECM/cell adhesion, signal transduction, and transcription. The ECM/cell adhesion genes that showed the largest differential expression (Log2FC ±1.5) were ADAM15, BGN, LDB3, and CRKL. ADAM15, which is a metalloproteinase that can bind integrins, was upregulated in high outflow regions, while the proteoglycan BGN and two genes associated with integrin signaling (LDB3, and CRKL) were downregulated. Immunolabeling studies supported the differential expression of ADAM15 and showed that it was specifically upregulated in high outflow regions along the inner wall of Schlemm’s canal and in the juxtacanalicular (JCT) region of the TM. In addition to these genes, the studies showed that genes for decorin, a small leucine-rich proteoglycan, and the α8 integrin subunit were enriched in high outflow regions. These studies identify several novel genes that could be involved in segmental outflow, thus demonstrating that digital spatial profiling could be a useful approach for understanding segmental flow through the TM. Furthermore, this study suggests that changes in the expression of genes involved in regulating the activity and/or organization of the ECM and integrins in the TM are likely to be key players in segmental outflow.

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Circumferential trabecular meshwork cell density in the human eye

Cited by 8 publications

References 29 publications

Changes to Outflow Structures After Pilocarpine in Primary Open Angle Glaucoma Compared With Healthy Individuals Using Optical Coherence Tomography

Changes to Outflow Structures After Pilocarpine in Primary Open Angle Glaucoma Compared With Healthy Individuals Using Optical Coherence Tomography

Tissue-engineered anterior segment eye cultures demonstrate hallmarks of conventional organ culture

Digital spatial profiling of segmental outflow regions in trabecular meshwork reveals a role for ADAM15

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