MMP Inhibition Preserves Integrin Ligation and FAK Activation to Induce Survival and Regeneration in RGCs Following Optic Nerve Damage
Bibliographic record
Abstract
Purpose: Integrin adherence to the extracellular matrix (ECM) is essential for retinal ganglion cell (RGC) survival: damage causes production and release of ECM degrading matrix metalloproteinases (MMPs) that disrupt integrin ligation, leading to RGC death. The interplay of MMPs, integrins, and focal adhesion kinase (FAK) was studied in RGCs after optic nerve injury. Methods: Optic nerve transection and optic nerve crush were used to study RGC survival and regeneration, respectively. Treatments were administered intravitreally or into the cut end of the optic nerve. RGC survival was assessed by fluorescence or confocal microscopy; cell counting, peptide levels, and localization were assessed by Western blot and immunohistochemistry. Results: MMP-9 was most strongly increased and localized to RGCs after injury. Pan-MMP, MMP-2/-9, and MMP-3 inhibition all significantly enhanced RGC survival and increased RGC axon regeneration. FAK activation was decreased at 4 days postaxotomy, when apoptosis begins. FAK inhibition reduced RGC survival and abrogated the neuroprotective effects of MMP inhibition, whereas FAK activation increased RGC survival despite MMP activation. Integrin ligation with CD29 antibody or glycine-arginine-glycine-aspatate-serine (GRGDS) peptide increased RGC survival after axotomy. Conclusions: ECM-integrin ligation promotes RGC survival and axon regeneration via FAK activation.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.002 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 teacher head, 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".