A mast cell stabilizer attenuates pathological angiogenesis in a model of choroidal neovascularization
Bibliographic record
Abstract
Age‐related macular degeneration (AMD) is one of the leading causes of irreversible blindness in the elderly worldwide. Wet AMD is characterized by pathologic choroidal neovascularization that invades the RPE and compromises retinal function. Although anti‐vascular endothelial growth factor (anti‐VEGF) therapy has been shown to improve symptoms of wet AMD in a large number of people, long‐term treatment is associated with the development of geographic atrophy. The development of new therapeutic alternatives to prevent the progression of exudative AMD is still necessary. Inflammation and deterioration of the RPE are considered to be the main sources of the pathogenesis of AMD. Recent studies have reported accumulation and degranulation of mast cells in the compromised choroid of patients with AMD. When activated, mast cells can secrete a variety of biologically active mediators, including inflammatory cytokines and proteolytic enzymes such as tryptase. However, the precise role of mast cells in the pathogenesis of AMD remains largely unknown. We are interested in how mast cells participate in the initiation of inflammation in the choroid which results in pathological choroidal neovascularization. We investigated the effect of a mast cell stabilizer on angiogenic response in the choroid. The angiogenic effect of a mast cell stabilizer, ketotifen fumarate, was evaluated in laser‐induced CNV model. Mice received intraperitoneal injections of ketotifen fumarate (5 and 25 mg/kg/d) or vehicle. CNV area and mononuclear phagocytes were determined respectively by using lectin staining and an anti–IBA‐1 antibody on RPE/choroid flat mounts. CNV was attenuated by ketotifen fumarate with no effect on inflammatory cell recruitment. Conditioned media from activated peritoneal mast cells exerted proangiogenic effects on vascular sprouting. Tryptase increased choroidal endothelial cell migration and choroidal vascular sprouting. The study supports possible modulation of mast cells as a therapeutic modality for CNV.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| 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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 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".