Retinal pigment epithelium cell‐derived microparticles mediate oxidative stress‐induced retinal cells dysfunction
Bibliographic record
Abstract
Abstract Purpose Age‐related macular degeneration (AMD) represents the leading cause of vision loss in the elderly. The cumulative oxidative injury induces retinal pigment epithelium (RPE) membrane microparticles production, RPE cell death and cellular senescence. The RPE blebs are implicated in the formation of sub‐retinal deposit. Nonetheless, the pathophysiological roles of RPE microparticles (RMPs) remain largely unexplored. This study was designed to investigate whether RMPs participate in the retinal cells dysfunction. Methods RMPs and fluorescent DiI‐labelled RMPs were isolated from cultured ARPE‐19 cells under oxidative stress. RMPs‐treated RPE cells were subjected to WST‐1, cellular senescent, apoptotic assay and FACS cell cycle analysis respectively. The antibody against CD36 was used in uptake experiment to determine the involvement of scavenger receptor CD36. Results Our study revealed that uptake of RMPs by RPE cells is time‐dependent, and this process is partially dependent on CD36 evidenced by an approximately 50% decrease of RMPs uptake caused by CD36 antibody treatment. In addition, RMPs significantly reduced RPE cell viability in a dose‐dependent manner. RMPs in a concentration of 5% µg/ml significantly induced RPE cell‐cycle arrest at G0/G1 phase. RMPs‐treated cells exhibited a 19% increase in G0/G1 phase, with associated increases of the senescence‐associated β‐galactosidase activity. Conclusion We demonstrated for the first time that RPE cells uptake microparticles derived from RPE cells under oxidative stress. These findings strongly suggest that RMPs function as mediators to exacerbate the oxidative damages to RPE cells, and indicate a pathological role of RMPs in AMD.
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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) | 0.005 | 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; both teacher heads agree on what is shown here.
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".