Sildenafil-mediated reduction in retinal function in heterozygous mice lacking the gamma-subunit of phosphodiesterase.
Bibliographic record
Abstract
PURPOSE: Retinitis pigmentosa (RP) is a common inherited degenerative retinal disease that has many causes including mutations in the genes coding for cyclic guanosine monophosphate (cGMP) phosphodiesterase 6 (PDE6). Sildenafil (Viagra; Pfizer Pharmaceuticals, New York, NY), a widely used medication for erectile dysfunction, is a specific inhibitor of PDE, with the potential to affect PDE6 in the retina. The purpose of this study was to investigate the retinal effects of sildenafil on knockout mice heterozygous for a mutation causing absence of the gamma subunit of rod PDE6 (PDEG:(tm1)/+). METHODS: Wild-type mice and PDEG:(tm1)/+ mice were subjected to electroretinography (ERG) 1 hour after exposure to one of three treatments: 1) no drug, 2) an intraperitoneal injection of sildenafil at 2 times the equivalent maximal daily recommended dosage for humans, or 3) 10 times this dosage. Control ERGs were also obtained to evaluate the reversibility of changes in retinal function after sildenafil treatment. A minimum of 48 hours elapsed between electroretinogram (ERG) recordings for drug washout and animal recovery. RESULTS: ERGs of the PDEG:(tm1)/+ mice treated with sildenafil showed a reversible, dose-dependent decrease in a- and b-wave amplitudes. Wild-type mice treated with sildenafil did not show significant differences in either a- or b-wave amplitudes compared with untreated control animals. CONCLUSIONS: These findings suggest that sildenafil has a significant impact on retinal function in PDEG:(tm1)/+ mice and may have implications in human carriers of RP. In addition, extension of these results in other model systems could be useful in understanding the mechanisms of RP and other forms of retinal degeneration.
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.
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) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 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; 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".