       Document 0141
 DOCN  M9640141
 TI    Inhibition of vascular endothelial growth factor prevents retinal
       ischemia-associated iris neovascularization in a nonhuman primate.
 DT    9604
 AU    Adamis AP; Shima DT; Tolentino MJ; Gragoudas ES; Ferrara N; Folkman J;
       D'Amore PA; Miller JW; Department of Opthalmology, Massachusetts Eye and
       Ear Infirmary,; Boston, USA.
 SO    Arch Ophthalmol. 1996 Jan;114(1):66-71. Unique Identifier : AIDSLINE
       MED/96133215
 AB    OBJECTIVE: To determine if the angiogenic peptide vascular endothelial
       growth factor (VEGF) is required for retinal ischemia-associated iris
       neovascularization in a nonhuman primate. METHODS: Laser retinal vein
       occlusion was used to produce retinal ischemia in 16 eyes of eight
       animals (Macaca fascicularis). Eyes were randomized to treatment every
       other day with intravitreal injections of either a neutralizing
       anti-VEGF monoclonal antibody or a control monoclonal antibody of the
       same isotype. Serial iris fluorescein angiograms were assessed using a
       standardized grading system and masked readers. Retinal VEGF and
       placental growth factor expression were assessed by Northern blotting.
       The specificity of the antibodies was determined in capillary
       endothelial cell proliferation assays prior to intravitreal injection.
       RESULTS: Zero of eight eyes receiving the neutralizing anti-VEGF
       antibodies developed iris neovascularization. Five of eight control
       antibody-treated eyes developed iris neovascularization. The difference
       was statistically significant (P = .03). Intravitreal antibody injection
       did not impair the ability of the ischemic retina to increase VEGF
       messenger RNA expression. The anti-VEGF antibodies specifically
       inhibited VEGF-driven capillary endothelial cell proliferation in vitro.
       CONCLUSION: These data demonstrate that VEGF is required for iris
       neovascularization in an adult nonhuman primate eye. The inhibition of
       VEGF is a new potential therapeutic strategy for the treatment of ocular
       neovascularization.
 DE    Animal  Antibodies, Monoclonal/PHARMACOLOGY  Blotting, Northern
       Capillary Permeability  Endothelial Growth Factors/*ANTAGONISTS &
       INHIB/IMMUNOLOGY/  PHYSIOLOGY  Fluorescein Angiography  HIV Envelope
       Protein gp120/IMMUNOLOGY  Iris/*BLOOD SUPPLY/PATHOLOGY
       Ischemia/*COMPLICATIONS/METABOLISM  Lymphokines/*ANTAGONISTS &
       INHIB/IMMUNOLOGY/PHYSIOLOGY  Macaca fascicularis  Neovascularization,
       Pathologic/ETIOLOGY/PATHOLOGY/*PREVENTION &  CONTROL  Pregnancy
       Proteins/METABOLISM  Random Allocation  Retina/METABOLISM  Retinal Vein
       Occlusion/*COMPLICATIONS/METABOLISM  RNA, Messenger/BIOSYNTHESIS
       Support, Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

