Stimulation of PAR2 during OIR reduces endothelial cell death and provokes rapid revascularization
Bibliographic record
Abstract
In the retina, a highly regulated vascular meshwork irrigates neurons and supplies necessary metabolic requirements. Sustained vessel loss, as in Retinopathy of Prematurity (ROP), prompts revascularization despite initial suppression of vaso‐survival cues such as VEGF. Thus, other forces are likely involved. Importantly, we have previously demonstrated the substantial role of Protease‐activated receptor 2 (PAR2), a GPCR, in the developing retina. The exact mechanism by which PAR‐2 modulates angiogenic cues in ROP remains elusive. Expression and localization of PAR2 was determined by Western blot and immunohistochemistry in mouse whole retina. Appraisal of retinal vasculature and expression of pro‐ and anti‐angiogenic cues was assessed following intravitreal administration of PAR2 agonist peptide (SLIGRL) or lentiviral shRNA knockdown of PAR2 (LV shPAR2) in mice exposed to a murine oxygen‐induced retinopathy model (75% O2 from P7‐P12). Our results demonstrate a pronounced expression of PAR2 preferentially in RGC. PAR2 sharply increases during the initial phases of vaso‐obliteration (VO) and during the neovascularization (NV) phase. Activation of PAR2 with SLIGRL in vivo reduced Sema3A while increasing VEGF. Importantly, SLIGRL treatment in vivo prior to and following oxygen exposure significantly decreased VO and NV. Treatment with LV shPAR2 increased VO while augmenting NV. This study underscores the importance of the coupling between neurons and vessels and shows that RGC‐specific PAR2 plays a pivotal role in modulating angiogenesis in a pathological context.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| 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".