Transgenic mice with increased expression of vascular endothelial growth factor in the retina: A new model of intraretinal and subretinal neovascularization

Naoyuki Okamoto, Takao Tobe, Sean F. Hackett, Hiroaki Ozaki, Melissa A. Vinores, William LaRochelle, Donald J Zack, Peter A Campochiaro

Research output: Contribution to journalArticle

Abstract

Vascular endothelial growth factor (VEGF) has been implicated in retinal neovascularization (NV), but it has been difficult to produce retinal NV with exogenous VEGF. We investigated the effect of increased VEGF expression in the retina using tissue-specific, gain-of-function transgenic mice in which the bovine rhodopsin promoter is coupled to the gene for human VEGF. Three founder mice were obtained and used to generate transgenic lines. One of the lines shows increased expression of VEGF in the retina by reverse transcription coupled to polymerase chain reaction and Northern blots, and the VEGF is localized to photoreceptors by immunohistochemistry. These mice demonstrate new vessels originating from the deep capillary bed of the retina that extend beneath the photoreceptor layer into the subretinal space where they form clumps of blood vessels surrounded by proliferated retinal pigmented epithelial cells. The appearance is similar to subretinal NV seen in some patients, except that the blood vessels originate from the retinal vasculature rather than the choroidal vasculature. One of the other two lines of mice did not show increased expression of VEGF and did not have NV; the other line showed retinal degeneration. This study demonstrates that overexpression of VEGF in the retina is sufficient to cause intraretinal and subretinal NV and provides a valuable new animal model.

Original languageEnglish (US)
Pages (from-to)281-291
Number of pages11
JournalAmerican Journal of Pathology
Volume151
Issue number1
StatePublished - 1997

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Vascular Endothelial Growth Factor A
Transgenic Mice
Retina
Retinal Neovascularization
Retinal Vessels
Retinal Degeneration
Rhodopsin
Northern Blotting
Reverse Transcription
Blood Vessels
Animal Models
Epithelial Cells
Immunohistochemistry
Polymerase Chain Reaction
Genes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Transgenic mice with increased expression of vascular endothelial growth factor in the retina : A new model of intraretinal and subretinal neovascularization. / Okamoto, Naoyuki; Tobe, Takao; Hackett, Sean F.; Ozaki, Hiroaki; Vinores, Melissa A.; LaRochelle, William; Zack, Donald J; Campochiaro, Peter A.

In: American Journal of Pathology, Vol. 151, No. 1, 1997, p. 281-291.

Research output: Contribution to journalArticle

Okamoto, Naoyuki ; Tobe, Takao ; Hackett, Sean F. ; Ozaki, Hiroaki ; Vinores, Melissa A. ; LaRochelle, William ; Zack, Donald J ; Campochiaro, Peter A. / Transgenic mice with increased expression of vascular endothelial growth factor in the retina : A new model of intraretinal and subretinal neovascularization. In: American Journal of Pathology. 1997 ; Vol. 151, No. 1. pp. 281-291.
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