Evidence map›Paper›PMID 35671048›Full record

ArticleInvestigative ophthalmology & visual science2022

Effect of SPARC Suppression in Mice, Perfused Human Anterior Segments, and Trabecular Meshwork Cells.

William W MacDonald, Swarup S Swaminathan, Jae Young Heo, Alexandra Castillejos, Jessica Hsueh, Brian J Liu, Diane Jo, Annie Du, Hyunpil Lee, Min Hyung Kang and 1 more

Open access · goldAbstract read
In one paragraph

Article in Investigative ophthalmology & visual science, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
1.0field-weighted citation impact, top 27% 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

2 citing papers in PubMed, 5 citations in OpenAlex.

  1. Article
  2. 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 2 institutions in 1 country.

William W MacDonaldDepartment of Ophthalmology & Visual Sciences, University Hospitals, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States.
Swarup S SwaminathanDepartment of Ophthalmology & Visual Sciences, University Hospitals, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States.
Jae Young HeoDepartment of Ophthalmology & Visual Sciences, University Hospitals, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States.
Alexandra CastillejosDepartment of Ophthalmology & Visual Sciences, University Hospitals, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States.
Jessica HsuehDepartment of Ophthalmology & Visual Sciences, University Hospitals, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States.
Brian J LiuDepartment of Ophthalmology & Visual Sciences, University Hospitals, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States.
Diane JoDepartment of Ophthalmology & Visual Sciences, University Hospitals, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States.
Annie DuDepartment of Ophthalmology & Visual Sciences, University Hospitals, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States.
Hyunpil LeeDepartment of Ophthalmology & Visual Sciences, University Hospitals, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States.
Min Hyung KangDepartment of Ophthalmology & Visual Sciences, University Hospitals, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States.
Douglas J RheeDepartment of Ophthalmology & Visual Sciences, University Hospitals, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States.
University School · USCase Western Reserve University · US

Funding

TISSUE CULTURE AND HYBRIDOMA MODULEP30EY011373 · NEI · CASE WESTERN RESERVE UNIVERSITY · PI Irina A Pikuleva · 1997 to 2026
$17.7M
P30 Core Grant for Vision ResearchP30EY014104 · NEI · MASSACHUSETTS EYE AND EAR INFIRMARY · PI Janey L Wiggs · 2002 to 2026
$15.1M
Matricellular Proteins in Trabecular Meshwork Increase Intraocular PressureR01EY019654 · NEI · MASSACHUSETTS EYE AND EAR INFIRMARY · PI RHEE, DOUGLAS J · 2009 to 2020
$3.5M
NEI NIH HHS P30 EY011373NEI NIH HHS P30 EY014104NEI NIH HHS R01 EY019654
6 · The paper itself

Abstract

Purpose: Secreted protein, acidic and rich in cysteine (SPARC) elevates intraocular pressure (IOP), increases certain structural extracellular matrix (ECM) proteins in the juxtacanalicular trabecular meshwork (JCT), and decreases matrix metalloproteinase (MMP) protein levels in trabecular meshwork (TM) endothelial cells. We investigated SPARC as a potential target for lowering IOP. We hypothesized that suppressing SPARC will decrease IOP, decrease structural JCT ECM proteins, and alter the levels of MMPs and/or their inhibitors. Methods: A lentivirus containing short hairpin RNA of human SPARC suppressed SPARC in mouse eyes and perfused cadaveric human anterior segments with subsequent IOP measurements. Immunohistochemistry determined structural correlates. Human TM cell cultures were treated with SPARC suppressing lentivirus. Quantitative reverse transcriptase polymerase chain reaction (PCR), immunoblotting, and zymography determined total RNA, relative protein levels, and MMP enzymatic activity, respectively. Results: Suppressing SPARC decreased IOP in mouse eyes and perfused human anterior segments by approximately 20%. Histologically, this correlated to a decrease in collagen I, IV, and VI in both the mouse TM and human JCT regions; in the mouse, fibronectin was also decreased but not in the human. In TM cells, collagen I and IV, fibronectin, MMP-2, and tissue inhibitor of MMP-1 were decreased. Messenger RNA of the aforementioned genes was not changed. Plasminogen activator inhibitor 1 (PAI-1) was upregulated in vitro by quantitative PCR and immunoblotting. MMP-1 activity was reduced in vitro by zymography. Conclusions: Suppressing SPARC decreased IOP in mice and perfused cadaveric human anterior segments corresponding to qualitative structural changes in the JCT ECM, which do not appear to be the result of transcription regulation.

Indexed as

FibronectinsTrabecular MeshworkAnimalsCadaverCollagen Type IEndothelial CellsExtracellular Matrix ProteinsHumansIntraocular PressureMatrix Metalloproteinase 1Matrix MetalloproteinasesMiceOsteonectinCollagen Type IExtracellular Matrix ProteinsFibronectinsMatrix Metalloproteinase 1Matrix MetalloproteinasesOsteonectinSPARC protein, humanSPARC protein, mouse

Identifiers

PMID35671048
PMCPMC9187959
OpenAlexW4281864020

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

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.