Vascular Endothelial Growth Factor Is Sufficient to Produce Iris Neovascularization and Neovascular Glaucoma in a Nonhuman Primate

doi:10.1001/archopht.1996.01100140172010

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Vol. 114 No. 8, August 1996

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Vascular Endothelial Growth Factor Is Sufficient to Produce Iris Neovascularization and Neovascular Glaucoma in a Nonhuman Primate

Michael J. Tolentino, MD; Joan W. Miller, MD; Evangelos S. Gragoudas, MD; Klio Chatzistefanou, MD; Napoleone Ferrara, MD; Anthony P. Adamis, MD

Arch Ophthalmol. 1996;114(8):964-970.

Abstract

Objective
To determine whether the angiogenic peptide vascular endothelialgrowth factor (VEGF) is sufficient to produce iris neovascularizationin a nonhuman primate (Macaca fascicularis).

Methods
Eight eyes of 4 animals were studied. The 165amino acid isoformof human recombinant VEGF (VEGF₁₆₅) was injected into the vitreousof 5 cynomolgus monkey eyes (doses ranging from 0.25-2.5 µgper injection). Equal amounts of inactivated human recombinantVEGF (2 eyes) or vehicle (1 eye) were injected into contralateralcontrol eyes. Eyes were assessed by slitlamp biomicroscopy,tonometry, iris color photography, fluorescein angiography,histopathologic examination, and immunostaining with antibodiesagainst proliferating cell nuclear antigen.

Results
All 5 bioactive VEGF-injected eyes developed neovascularizationwith dilated and tortuous iris vessels that leaked fluorescein.None of the 3 control eyes exhibited any iris vascular changes.Inflammation was absent in both treatment groups. A dose responseto VEGF was observed in the single animal that received 2.5µg and 0.25 µg in the right and left eyes, respectively.Iris vessel endothelial cells were positive for proliferatingcell nuclear antigen in the bioactive VEGF-injected eyes only.Injections of 1.25 µg of VEGF every 3 days during a 30-dayperiod produced advanced iris neovascularization, ectropionuvea, and neovascular glaucoma.

Conclusions
Intravitreal injections of recombinant human VEGF₁₆₅ in amountscomparable with those 165 sured in eyes with active neovascularizationare sufficient to produce noninflammatory iris neovascularizationin a nonhuman primate. Prolonged exposure to VEGF₁₆₅ can produceectropion uveae and neovascular glaucoma.

Author Affiliations

From the Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston (Drs Tolentino, Miller, Gragoudas, Chatzistefanou, and Adamis); Laboratory for Surgical Research, Department of Surgery, Children's Hospital, Boston (Drs Tolentino, Chatzistefanou, and Adamis); and Genentech Inc, South San Francisco, Calif (Dr Ferrara).

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