The Role of Lysophosphatidic Acid Receptor (LPA<sub>1</sub>) in the Oxygen-Induced Retinal Ganglion Cell Degeneration
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
PURPOSE: Although previous studies have demonstrated that hypoxia induces retinal ganglion cell (RGC) apoptosis and that transient retinal ischemia upregulates the expression of lysophosphatidic acid (LPA) receptors, it remains to be determined whether LPA(1) receptor mediates RGC degeneration during retinopathy of prematurity (ROP). By using an immortalized RGC line (RGC-5), primary neonatal RGC cultures, and oxygen-induced retinopathy (OIR) to model ROP, the authors explored whether LPA(1) receptor induces RGC degeneration and the potential mechanisms thereof. METHODS: OIR was induced by exposing rat pups to alternating cycles of hyperoxia/hypoxia from postnatal day (P) 0 to P14. RGC viability was evaluated by Fluorogold labeling. Effects of hyperoxia or hypoxia on LPA(1) expression were determined in the RGC-5 line by Western blot. Roles of hypoxia, LPA(1) receptor (with agonist, stearoyl-LPA; antagonist, THG1603; LPA(1) knock-down, shRNA-LPA(1)), and Rho kinase (with inhibitor Y-27632) in mediating RGC survival and neurite outgrowth were assessed by MTT assay and phase-contrast microscopy, respectively. Expression of GFP-LPA(1) in RGC-5 under hypoxia was examined by confocal microscopy. RESULTS: OIR caused pronounced RGC loss in the retina. LPA(1) receptor was expressed by RGCs in retinal tissue, whereas oxygen stress induced its expression in RGC-5. Exposure to stearoyl-LPA or hypoxia substantially reduced the viability of RGCs; this was abrogated by THG1603 and shRNA-LPA(1). THG1603 and Y-27632 treatment also attenuated the adverse effects of hypoxia on RGC-5 neurite outgrowth, and their intravitreal administration prevented OIR-induced RGC loss. Interestingly, overexpression of LPA(1) increased RGC-5 susceptibility to hypoxia-induced cell loss. CONCLUSIONS: Current data strongly support a critical role for LPA(1) receptor in mediating RGC degeneration during OIR.
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.
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 | 0.002 | 0.001 |
| 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 | 0.000 |
| Open science | 0.001 | 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 it