학술논문

Vascular endothelial growth factor and the potential therapeutic use of pegaptanib (macugen) in diabetic retinopathy.
Document Type
Academic Journal
Author
Starita C; Pfizer Ltd., Sandwich, UK.; Patel MKatz BAdamis AP
Source
Publisher: Karger Country of Publication: Switzerland NLM ID: 8010321 Publication Model: Print Cited Medium: Print ISSN: 0250-3751 (Print) Linking ISSN: 02503751 NLM ISO Abbreviation: Dev Ophthalmol Subsets: MEDLINE
Subject
Language
English
ISSN
0250-3751
Abstract
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.