Altered expression of transforming growth factor beta 1 and matrix metalloproteinase-9 results in elevated intraocular pressure in mice.
Bibliographic record
Abstract
PURPOSE: Extracellular matrix remodeling is thought to have profound effects on tissue architecture and associated function. We have shown previously that overexpression of transforming growth factor beta (TGFβ), which stimulates matrix accumulation, results in altered morphology, cataract, and ocular hypertension in rodents. We have further shown that TGFβ-induced cataracts can be mitigated through inhibition of the matrix metalloproteinases (MMP) MMP-2 and MMP-9. We therefore sought to determine whether loss of MMP expression also altered TGFβ-induced changes in intraocular pressure (IOP). METHODS: To carry out this study, TGFβ1 transgenic mice were bred onto a MMP-9 null background. IOP measurements were made at 1- to 2-, 2- to 3-, and 3- to 4-month time points using a TonoLab rebound tonometer. Histological and immunofluorescence findings were obtained at the same time points. RESULTS: Our results demonstrate that lens-specific expression of TGFβ1 in mice results in altered morphology of the anterior segment and an accompanying significant increase in IOP. TGFβ1 transgenic mice bred onto the MMP-9 null background exhibited a further increase in IOP. Interestingly, the MMP-9-deficient animals (without the TGFβ transgene), which exhibited normal angle morphology, had increased IOP levels compared to their wild-type littermates. CONCLUSION: These results indicate that TGFβ and MMP-9 likely act independently in regulating IOP. Additionally, MMP-9 plays an important role in maintaining IOP, and further investigation into the mechanisms of MMP-9 activity in the anterior angle may give clues to how extracellular matrix remodeling participates in ocular hypertension and glaucoma.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".