Amphiregulin and Growth Differentiation Factor 11 Promote Retinal Ganglion Cell Survival In Vivo through Activation of Smad3
Bibliographic record
Abstract
Although adult neurons in the mammalian central nervous system (CNS) cannot spontaneously repair themselves after injury, a growing body of evidence indicates that genetically manipulating them can increase their intrinsic reparative ability.However, as genetic manipulation is not clinically feasible, current research continues to investigate pharmacological approaches to transiently enhance the intrinsic ability of adult CNS neurons to survive and regenerate their axons.Amphiregulin (AREG) is a unique epidermal growth factor receptor (EGFR) ligand that has been shown to be crucial in liver regeneration, and accumulating evidence suggests that AREG signaling can promote both survival and axon regeneration of neurons.Growth differentiation factor 11 (GDF11) is a member of the transforming growth factor β (TGF-β) superfamily, and it has been shown to exert rejuvenation effects in the aged brain and promote neuronal survival in the CNS.However, it is unknown whether AREG and GDF11 are capable of inducing neuronal survival and axon regeneration in the visual system.Hence, the current study investigated: 1) the developmental and post-injury expression patterns of these two ligands and their respective receptors, EGFR and activin-like kinase 5 (ALK5), 2) the potential neuroprotective and regenerative effects of these two ligands on retinal ganglion cells (RGCs) by using optic nerve crush (ONC) model, and 3) the molecular mechanisms mediating the neuroprotective and regenerative effects of AREG and GDF11 on RGCs.Based on the western blot and immunohistochemical data, both AREG and GDF11 are consistently expressed throughout retina development, but their receptors are only upregulated during early retina development.Furthermore, AREG expression is significantly reduced in adult retina 7 days after ONC whereas GDF11 expression remains unchanged after ONC.Interestingly, while EGFR expression is only upregulated 3 days after ONC, ALK5 expression is consistently upregulated throughout the v
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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) | 0.000 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".