Activation of the Extracellular Signal-Regulated Kinase 1/2 Pathway by AAV Gene Transfer Protects Retinal Ganglion Cells in Glaucoma
Why this work is in the frame
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Bibliographic record
Abstract
Glaucoma is the second leading cause of blindness in the world. Loss of vision in glaucomatous optic neuropathy is caused by the selective degeneration of retinal ganglion cells (RGCs). Ocular hypertension is a major risk factor in glaucoma, but visual field defects continue to progress in some patients despite the use of drugs that lower intraocular pressure. At present, there are no effective neuroprotective strategies for the treatment of this disease. The extracellular signal-regulated kinase (Erk) 1/2 pathway is an evolutionarily conserved mechanism used by several peptide factors to promote cell survival. Here we tested if selective activation of Erk1/2 protected RGCs in a rat model of experimental glaucoma. We used recombinant adeno-associated virus to transduce RGCs with genes encoding constitutively active or wild-type MEK1 (approved gene symbol MAP2K1), the upstream activator of Erk1/2. MEK1 gene transfer into RGCs markedly increased neuronal survival: 1366 +/- 70 RGCs/mm(2) (mean +/- SEM) were alive in the dorsal retina at 5 weeks after ocular hypertension surgery, a time when only 680 +/- 86 RGCs/mm(2) of these neurons remained in control eyes. We conclude that the Erk1/2 pathway plays a key role in the protection of RGCs from ocular hypertensive damage. This study identifies a novel gene therapy strategy in which selective activation of the Erk1/2 signaling pathway effectively slows cell death in glaucoma.
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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 it