Exploring Current Molecular Targets in the Treatment of Neovascular Age-Related Macular Degeneration toward the Perspective of Long-Term Agents
Abstract
:1. Introduction
2. Molecular Pathways Involved in Macular Neovascularization
2.1. An Overview of Angiogenic Factors Involved in Angiogenesis
2.2. Mediators Isolated in Neovascular Membranes Secondary to AMD
2.3. Angiogenesis and Arteriogenesis in the Pathogenesis of Neovascular Membranes
3. Current Anti-VEGF Therapies for MNV
3.1. Bevacizumab
3.2. Ranibizumab
3.3. Aflibercept
3.4. Brolucizumab
3.5. Faricimab
4. Strategies to Achieve Sustained Disease Control in AMD
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Ligands | Receptor | Biological Function | Role in AMD |
---|---|---|---|
VEGFA | VEGFR1, VEGFR2 |
| New vessel formation in NV Fluid extravasation Support of neovascular membrane Inflammatory response |
PlGF | VEGFR1 |
| Stimulate vessel growth and remodeling of NV Vessel maturation |
VEGFB | VEGFR1 |
| Stimulate vessel growth and remodeling of NV |
VEGFC | VEGFR2, VEGFR3 | Regulates lymphatic vessels | None |
VEGFD | VEGFR2, VEGFR3 | Regulates lymphatic vessels | None |
Characteristics | Bevacizumab | Ranizibumab | Aflibercept | Brolucizumab | Faricimab |
---|---|---|---|---|---|
Class | Monoclonal Ab | Fab fragment | Fusion protein | scFv | Monoclonal Ab bispecific |
Target | VEGFA | VEGFA | VEGFA, PlGF, VEGFB, galectin-1 | VEGFA | VEGFA, Ang-2 |
Dose | 1.25 mg | 0.5 mg | 2 mg | 6 mg | 6 mg |
Molecular weight | 149 kDa | 48 kDa | 115 kDa | 26 kDa | 150 kDa |
Dissociation constant | 58 pM | 46 pM | 0.49 pM | 28.4 pM | 3 nM |
Vitreous half-life (days) | 4.9 | 9 | 9.1 | 3.1 | 7.5 |
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Fragiotta, S.; Bassis, L.; Abdolrahimzadeh, B.; Marino, A.; Sepe, M.; Abdolrahimzadeh, S. Exploring Current Molecular Targets in the Treatment of Neovascular Age-Related Macular Degeneration toward the Perspective of Long-Term Agents. Int. J. Mol. Sci. 2024, 25, 4433. https://doi.org/10.3390/ijms25084433
Fragiotta S, Bassis L, Abdolrahimzadeh B, Marino A, Sepe M, Abdolrahimzadeh S. Exploring Current Molecular Targets in the Treatment of Neovascular Age-Related Macular Degeneration toward the Perspective of Long-Term Agents. International Journal of Molecular Sciences. 2024; 25(8):4433. https://doi.org/10.3390/ijms25084433
Chicago/Turabian StyleFragiotta, Serena, Lorena Bassis, Barmak Abdolrahimzadeh, Alessandra Marino, Massimiliano Sepe, and Solmaz Abdolrahimzadeh. 2024. "Exploring Current Molecular Targets in the Treatment of Neovascular Age-Related Macular Degeneration toward the Perspective of Long-Term Agents" International Journal of Molecular Sciences 25, no. 8: 4433. https://doi.org/10.3390/ijms25084433