Evidence map›Paper›PMID 33516765›Full record

ArticleExperimental eye research2021

A tissue-engineered human trabecular meshwork hydrogel for advanced glaucoma disease modeling.

Haiyan Li, Tyler Bagué, Alexander Kirschner, Ana N Strat, Haven Roberts, Robert W Weisenthal, Alison E Patteson, Nasim Annabi, W Daniel Stamer, Preethi S Ganapathy and 1 more

Open access · greenAbstract read
In one paragraph

Article in Experimental eye research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed, 1 pooled it
8.0field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

32 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.

  1. Pooled it
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  8. Considerations and implications of currentFrontiers in cell and developmental biology · 2025
    Review
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  18. Long non-coding RNA SNHG11 regulates the Wnt/β-catenin signaling pathway through rho/ROCK in trabecular meshwork cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023
    Article
  19. Article
  20. iPSCs-Based Therapy for Trabecular Meshwork.Handbook of experimental pharmacology · 2023
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 4 institutions in 1 country.

Haiyan LiDepartment of Ophthalmology and Visual Sciences, SUNY Upstate Medical University, Syracuse, NY, 13210, USA; Department of Cell and Developmental Biology, SUNY Upstate Medical University, Syracuse, NY, 13210, USA; BioInspired Institute, Syracuse University, Syracuse, NY, 13244, USA.
Tyler BaguéDepartment of Ophthalmology and Visual Sciences, SUNY Upstate Medical University, Syracuse, NY, 13210, USA.
Alexander KirschnerDepartment of Ophthalmology and Visual Sciences, SUNY Upstate Medical University, Syracuse, NY, 13210, USA.
Ana N StratDepartment of Ophthalmology and Visual Sciences, SUNY Upstate Medical University, Syracuse, NY, 13210, USA.
Haven RobertsDuke Eye Center, Duke University, Durham, NC, 27708, USA.
Robert W WeisenthalDepartment of Ophthalmology and Visual Sciences, SUNY Upstate Medical University, Syracuse, NY, 13210, USA.
Alison E PattesonBioInspired Institute, Syracuse University, Syracuse, NY, 13244, USA; Department of Physics, Syracuse University, Syracuse, NY, 13244, USA.
Nasim AnnabiDepartment of Chemical and Biomolecular Engineering, University of California Los Angeles, Los Angeles, CA, 90095, USA.
W Daniel StamerDuke Eye Center, Duke University, Durham, NC, 27708, USA.
Preethi S GanapathyDepartment of Ophthalmology and Visual Sciences, SUNY Upstate Medical University, Syracuse, NY, 13210, USA; BioInspired Institute, Syracuse University, Syracuse, NY, 13244, USA; Department of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, NY, 13210, USA.
Samuel HerbergDepartment of Ophthalmology and Visual Sciences, SUNY Upstate Medical University, Syracuse, NY, 13210, USA; Department of Cell and Developmental Biology, SUNY Upstate Medical University, Syracuse, NY, 13210, USA; BioInspired Institute, Syracuse University, Syracuse, NY, 13244, USA; Department of Biochemistry and Molecular Biology, SUNY Upstate Medical University, Syracuse, NY, 13210, USA; Department of Biomedical and Chemical Engineering, Syracuse University, Syracuse, NY, 13244, USA. Electronic address: herbergs@upstate.edu.
SUNY Upstate Medical University · USDuke University · USSyracuse University · USUniversity of California, Los Angeles · US

Funding

Caveolae-Based Mechanosensors for Conventional Outflow RegulationR01EY028608 · NEI · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI MICHAEL H ELLIOTT, W Daniel Stamer · 2018 to 2026
$3.8M
Molecular Mechanisms of Exfoliation GlaucomaR01EY030617 · NEI · DUKE UNIVERSITY · PI HAUSER, MICHAEL A, STAMER, W DANIEL · 2019 to 2023
$2.8M
Engineering highly elastic surgical sealants with hemostatic propertiesR01HL140618 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ANNABI, NASIM, KHADEMHOSSEINI, ALI · 2018 to 2021
$2.8M
Engineering a naturally derived and highly adhesive surgical sealantR01EB023052 · NIBIB · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ANNABI, NASIM, KHADEMHOSSEINI, ALI · 2017 to 2022
$2.4M
Transcriptional and Biomechanical Analysis of Segmental Outflow in GlaucomaR01EY031710 · NEI · GEORGIA INSTITUTE OF TECHNOLOGY · PI ETHIER, C ROSS, GUPTA, DIVAKAR · 2020 to 2023
$2.4M
American Heart Association-American Stroke Association 16SDG31280010NEI NIH HHS R01 EY028608NEI NIH HHS R01 EY030617NEI NIH HHS R01 EY031710NHLBI NIH HHS R01 HL140618NIBIB NIH HHS R01 EB023052
6 · The paper itself

Abstract

Abnormal human trabecular meshwork (HTM) cell function and extracellular matrix (ECM) remodeling contribute to HTM stiffening in primary open-angle glaucoma (POAG). Most current cellular HTM model systems do not sufficiently replicate the complex native three dimensional (3D) cell-ECM interface, limiting their use for investigating POAG pathology. Tissue-engineered hydrogels are ideally positioned to overcome shortcomings of current models. Here, we report a novel biomimetic HTM hydrogel and test its utility as a POAG disease model. HTM hydrogels were engineered by mixing normal donor-derived HTM cells with collagen type I, elastin-like polypeptide and hyaluronic acid, each containing photoactive functional groups, followed by UV crosslinking. Glaucomatous conditions were induced with dexamethasone (DEX), and effects of the Rho-associated kinase (ROCK) inhibitor Y27632 on cytoskeletal organization and tissue-level function, contingent on HTM cell-ECM interactions, were assessed. DEX exposure increased HTM hydrogel contractility, f-actin and alpha smooth muscle actin abundance and rearrangement, ECM remodeling, and fibronectin deposition - all contributing to HTM hydrogel condensation and stiffening consistent with glaucomatous HTM tissue behavior. Y27632 treatment produced precisely the opposite effects and attenuated the DEX-induced pathologic changes, resulting in HTM hydrogel relaxation and softening. For model validation, confirmed glaucomatous HTM (GTM) cells were encapsulated; GTM hydrogels showed increased contractility, fibronectin deposition, and stiffening vs. normal HTM hydrogels despite reduced GTM cell proliferation. We have developed a biomimetic HTM hydrogel model for detailed investigation of 3D cell-ECM interactions under normal and simulated glaucomatous conditions. Its bidirectional responsiveness to pharmacological challenge and rescue suggests promising potential to serve as screening platform for new POAG treatments with focus on HTM biomechanics.

Indexed as

HydrogelsModels, BiologicalActinsAged, 80 and overAmidesBiomimetic MaterialsCytoskeletal ProteinsDexamethasoneElastinEnzyme InhibitorsEye ProteinsFemaleGene Expression RegulationGlaucoma, Open-AngleGlucocorticoidsGlycoproteinsActinsAmidesCytoskeletal ProteinsDexamethasoneElastinELN protein, humanEnzyme InhibitorsEye ProteinsGlucocorticoidsGlycoproteinsHydrogelsMyocilinPyridinesrho-Associated KinasesY 27632BioengineeringECM mechanicsIn vitroPOAGTissue stiffening

Identifiers

PMID33516765
PMCPMC11097970
OpenAlexW3129042037

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.