VEGF (Vascular Endothelial Growth Factor)
Central target in retinal disease — necessary and sufficient for both vessel leakage and neovascularization. Career-defining work of Anthony Adamis and Napoleon Ferrara (Genentech). Discussed at Session VII.
Anti-VEGF Therapy
- Ranibizumab (Lucentis): 20–25 letter treatment delta in Phase 3 — unmatched in 25 years
- Countries that adopted anti-VEGF: ~50% reduction in blindness rates
- But the ceiling arrived: ~half of patients achieve complete fluid resolution; ~half have residual fluid despite optimal therapy
Beyond VEGF
The next generation of retinal drugs activates repair pathways rather than blocking pathology:
- TIE2 agonism (Tiespectus) — restores endothelial integrity
- Wnt/Frizzled-4 agonism (Restoret) — rebuilds the blood-retinal barrier itself
Three Layers of Vascular Biology
| Pathway | Role |
|---|---|
| VEGF | Triggers pathology — leakage, barrier breakdown, neovascularization |
| TIE2 | Repair — restores endothelial integrity, reconstitutes pericyte support |
| Wnt/Frizzled-4 | Encodes the blood-retinal barrier itself |
See also: tie2
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