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Record W2269181593 · doi:10.1111/j.1755-3768.2015.0546

<scp>MMP</scp>‐9 null mice display elevated <scp>IOP</scp> due to reduced aqueous humor drainage from the trabecular meshwork

2015· article· en· W2269181593 on OpenAlexaff
Lies De Groef, Anuja Siwakoti, Emiel Geeraerts, Johan Billen, Ingeborg Stalmans, Judith A. West‐Mays, Lieve Moons

Bibliographic record

VenueActa Ophthalmologica · 2015
Typearticle
Languageen
FieldMedicine
TopicGlaucoma and retinal disorders
Canadian institutionsMcMaster University
Fundersnot available
KeywordsTrabecular meshworkAqueous humorMatrix metalloproteinaseOphthalmologyIntraocular pressureNull (SQL)Aqueous humourMedicineGlaucomaDrainageChemistryBiologyInternal medicineComputer science

Abstract

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Purpose Aqueous humor outflow resistance depends on a complex equilibrium of extracellular matrix biosynthesis versus proteolysis in the trabecular meshwork. Several members of the MMP family, including MMP ‐9, are essential to the regulation of aqueous humor outflow resistance, i.e . to intraocular pressure ( IOP ) homeostasis. Here, we characterized the baseline ocular phenotype of MMP ‐9 null mice, with emphasis on the dysregulation of IOP homeostasis. Methods MMP ‐9 null and wild type mice, from 3 to 13 months of age, were studied. IOP and central corneal thickness were measured via rebound tonometry and pachymetry, resp. Anterior chamber morphology and trabecular meshwork organization were studied (1) in vivo with OCT , (2) via light microscopy and (3) by means of transmission electron microscopy ( TEM ), and its collagen composition was studied using Sirius Red and immunostainings. Integrity of the retina and optic nerve were evaluated with OCT and histological stainings on tissue sections and retinal flatmounts. Results MMP ‐9 null mice present with early‐onset ocular hypertension, and fluorophotometric measurements of aqueous humor turnover revealed a reduced aqueous humor drainage. While OCT , light microscopy and TEM analysis did not disclose any abnormalities in the cellular organization of the trabecular meshwork, collagen staining indicated that there is an aberrant extracellular matrix composition in MMP ‐9 null mice. Remarkably, the observed IOP elevation in MMP ‐9 null mice did not result in a glaucomatous phenotype at the level of the retina and optic nerve at the ages studied. Conclusions Our observations corroborate the role of MMP ‐9 as an important remodeler of the trabecular meshwork, and evidence for a causal link between MMP ‐9 deficiency, trabecular meshwork composition and IOP elevation is revealed.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.006
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.688
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.006
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0000.001

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.027
GPT teacher head0.273
Teacher spread0.246 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2015
Admission routes1
Has abstractyes

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