Evidence map›Paper›PMID 25103269›Full record

ArticleInvestigative ophthalmology & visual science2014

Differential effects of caveolin-1 and -2 knockdown on aqueous outflow and altered extracellular matrix turnover in caveolin-silenced trabecular meshwork cells.

Mini Aga, John M Bradley, Rohan Wanchu, Yong-feng Yang, Ted S Acott, Kate E Keller

Open access · hybridAbstract read
In one paragraph

Article in Investigative ophthalmology & visual science, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
3.6field-weighted citation impact, top 7% 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

37 citing papers in PubMed, 63 citations in OpenAlex.

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  12. Normal and glaucomatous outflow regulation.Progress in retinal and eye research · 2021
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  19. Molecular taxonomy of human ocular outflow tissues defined by single-cell transcriptomics.Proceedings of the National Academy of Sciences of the United States of America · 2020
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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

6 authors at 1 institution in 1 country.

Mini AgaCasey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States.
John M BradleyCasey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States.
Rohan WanchuCasey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States.
Yong-feng YangCasey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States.
Ted S AcottCasey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States.
Kate E KellerCasey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States.
Oregon Health & Science University · US

Funding

Proteomics CoreP30EY010572 · NEI · OREGON HEALTH & SCIENCE UNIVERSITY · PI Kate E Keller · 1995 to 2026
$19.4M
BIOLOGY OF TRABECULAR RESPONSE TO LASER TRABECULOPLASTYR01EY008247 · NEI · OREGON HEALTH & SCIENCE UNIVERSITY · PI ACOTT, TED S · 1989 to 2017
$7.7M
VERTEBRATE EYE: STUDIES OF AQUEOUS OUTFLOWR01EY003279 · NEI · OREGON HEALTH & SCIENCE UNIVERSITY · PI ACOTT, TED S · 1985 to 2012
$5.5M
Extracellular Matrix and Outflow ResistanceR01EY019643 · NEI · OREGON HEALTH & SCIENCE UNIVERSITY · PI KELLER, KATE E · 2010 to 2025
$5.0M
NEI NIH HHS EY003279NEI NIH HHS EY008247NEI NIH HHS EY010572NEI NIH HHS EY019643NEI NIH HHS P30 EY010572NEI NIH HHS R01 EY003279NEI NIH HHS R01 EY008247NEI NIH HHS R01 EY019643
6 · The paper itself

Abstract

purposeA single nucleotide polymorphism (SNP) identified between caveolin-1 (CAV1) and caveolin-2 (CAV2) on chromosome 7 is associated with glaucoma. One function of CAVs is endocytosis and recycling of extracellular matrix (ECM) components. Here, we generated CAV-silencing lentivirus to evaluate the effects on ECM turnover by trabecular meshwork (TM) cells and to measure the effect on outflow facility in anterior segment perfusion culture.

methodsShort hairpin CAV1 and CAV2 silencing and control lentivirus were generated, characterized, and applied to anterior segments in perfusion culture. Colocalization of CAVs with various ECM molecules in TM cells was investigated using immunofluorescence and confocal microscopy. Western immunoblotting and fluorogenic-based enzyme activity assays were used to investigate ECM protein levels and degradation, respectively.

resultsEndogenous CAVs colocalized with cortactin at podosome- or invadopodia-like structures (PILS), which are areas of focal ECM degradation. In perfusion culture, outflow rates increased significantly in CAV1-silenced anterior segments, whereas outflow significantly decreased in CAV2-silenced anterior segments. Matrix metalloproteinase (MMP)2 and MMP14, and a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS4) colocalized with both CAVs in TM cells. Protein levels and enzyme activities of MMP/ADAMTS4, fibronectin protein levels, actin stress fibers, and α-smooth muscle actin were all increased in CAV-silenced cells.

conclusionsCaveolin-mediated endocytosis is one mechanism by which TM cells can alter the physiological catabolism of ECM in order to change the composition of the outflow channels in the TM to regulate aqueous outflow resistance. Dysregulation of CAV function could contribute to the pathological changes in ECM that are observed in glaucoma.

Indexed as

ADAM ProteinsADAMTS4 ProteinAnalysis of VarianceAnterior Eye SegmentBiomarkersCaveolin 1Caveolin 2Extracellular MatrixFibronectinsGene SilencingGlaucoma, Open-AngleHumansMatrix Metalloproteinase 1Procollagen N-EndopeptidaseTrabecular MeshworkADAM ProteinsADAMTS4 ProteinADAMTS4 protein, humanBiomarkersCaveolin 1Caveolin 2FibronectinsMatrix Metalloproteinase 1Procollagen N-Endopeptidaseendocytosisextracellular matrixglaucoma anterior segmentmatrix metalloproteinasestrabecular meshwork

Identifiers

PMID25103269
PMCPMC4152152
OpenAlexW1969540652

What OpenQuestion holds

Textmetadata
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.