Pegaptanib sodium injection (
Macugen, Eyetech
Pharmaceuticals, Pfizer, New York, NY, USA) is a relatively new medication intended to treat the so-called wet (neovascular ) form of
age-related macular degeneration (AMD). This form of AMD is characterized by the growth of unwanted new blood vessels into the macula (angiogenesis). The aqueous
solution containing
pegaptanib is injected into the vitreous of the eye, where it binds to the 165
amino acid isoform of
vascular endothelial growth factor (
VEGF), a secreted
protein that is thought to play a major role in the
pathologic angiogenesis that occurs in wet AMD. Neovascular AMD is the leading cause of severe vision loss in people over age 60 in the United States and other industrialized countries (1).
Pegaptanib acts as a selective
VEGF antagonist through its molecular structure as an aptamer, a pegylated modified
oligonucleotide that adopts a three-dimensional configuration, enabling it to bind to extracellular
VEGF (Fig. 1). Aptamers are macromolecules composed of chemically synthesized single-stranded
nucleic acids (either
RNA or
DNA) that bind with a high degree of selectivity and affinity when exposed to target
proteins.
Pegaptanib binds VEGF165, and bound VEGF165 is not able to bind to the
VEGF receptor, thereby negating its ability to cause angiogenesis and vascular permeability. Other aptamers exist, as do other forms of treatment for AMD. To date, however, no treatment for AMD has allowed for better vision
after treatment, with most surgical treatments leading to almost immediate loss of some vision in the expectation of preventing more severe loss. Research in the field of
macular degeneration is advancing rapidly, and treatment with an aptamer such as
pegaptanib is a viable option despite the possibility of adverse events.