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Vascular endothelial growth factor and age-related macular degeneration: from basic science to therapy

Nature Medicine volume 16, pages 1107–1111 (2010)Cite this article

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It is almost intuitive that blood vessels have a central role in biology and medicine. Indeed, even though the concept of blood circulation was not established until a few centuries ago, mankind had known for millennia that blood vessels are indispensable for bringing nourishment to organs and limbs. The converse notion—that growth of blood vessels can promote or facilitate disease—is much more recent. Starting in the mid-nineteenth century, several investigators, including Rudolf Virchow, noted that tumor growth is frequently accompanied by increased vascularity1. Major conceptual advances took place in the 1930s and 1940s, when it was hypothesized that the ability to induce new vessel growth through release of vasoproliferative factors confers a growth advantage on tumor cells2,3.

At about the same time, seminal observations implicating blood-vessel growth in intraocular disorders leading to blindness were made. In 1948, Isaac Michaelson proposed, on the basis of his elegant embryologic and clinicopathological studies, that a diffusible factor (named afterward 'factor X') could be responsible not only for the development of the normal retinal vasculature but also for pathological neovascularization in proliferative diabetic retinopathy and other disorders4.

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Figure 1: Structure of the VEGF-ranibizumab complex, showing two Fab molecules binding the symmetrical poles of the VEGR dimer40.
Figure 2: Mean change from baseline visual acuity score (letters) over time in the ANCHOR trial.
Figure 3: Role of VEGF in the progression of CNV in wet AMD.

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Acknowledgements

It would be difficult to name all the contributors to a program that began 15 years ago. I thank all the ranibizumab team members. I wish to thank my current and former lab members. I am especially grateful to the following past and present colleagues and collaborators: H. Lowman, L. Presta, A. Cuthbertson, T. Adamis, J. Miller, L. D'Amico, R. Kim, T. Ianchulev & K. Hillan. I also wish to thank the ranibizumab clinical investigators. I thank my wife, Chika, for her understanding and support. I wish to express my sincere gratitude to the Lasker Foundation for conferring on me such a wonderful and prestigious award that I accept on behalf of my colleagues.

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  1. Napoleone Ferrara is at Genentech, South San Francisco, California, USA.,

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Correspondence to Napoleone Ferrara.

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N.F. is an employee of Genentech.

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Ferrara, N. Vascular endothelial growth factor and age-related macular degeneration: from basic science to therapy. Nat Med 16, 1107–1111 (2010). https://doi.org/10.1038/nm1010-1107

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