Vascular endothelial growth factor and the potential therapeutic use of pegaptanib (macugen) in diabetic retinopathy.
Both clinical and preclinical findings have implicated vascular endothelial growth factor (VEGF) in the pathophysiology of diabetic macular edema (DME). VEGF is both a potent enhancer of vascular permeability and a key inducer of angiogenesis. VEGF levels are elevated in the eyes of patients with DME, and in animal models of diabetes this elevation coincides with the breakdown of the blood-retinal barrier. Moreover, injection of VEGF (the VEGF165 isoform in particular) into healthy eyes of animals can induce diabetes-associated ocular pathologies.Pegaptanib, a novel RNA aptamer currently used in the treatment of agerelated macular degeneration, binds and inactivates VEGF165 and has been shown in animal models to reverse the blood-retinal barrier breakdown associated with diabetes. These findings formed the basis of a phase II trial involving 172 patients with DME, in which intravitreous pegaptanib (0.3 mg, 1 mg, 3 mg) or sham injections were administered every 6 weeks for 12 weeks, with the option of continuing for 18 more weeks or undergoing laser treatment. Compared to sham, patients receiving 0.3 mg displayed superior visual acuity (p = 0.04) as well as a reduction in retinal thickness of 68 micrometers compared to a slight increase under sham treatment (p = 0.021). These data support the use of pegaptanib in the treatment of DME.
Starita
Carla
C
Pfizer Ltd., Sandwich, UK.
Patel
Manju
M
Katz
Barrett
B
Adamis
Anthony P
AP
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D052157:Aptamers, Nucleotide / Q000627:therapeutic use*; D001813:Blood-Retinal Barrier / Q000502:physiology; D003930:Diabetic Retinopathy / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D014792:Visual Acuity
D020533:Angiogenesis Inhibitors; D052157:Aptamers, Nucleotide; D042461:Vascular Endothelial Growth Factor A; C495058:pegaptanib