Intrachoroidal neovascularization in transgenic mice overexpressing vascular endothelial growth factor in the retinal pigment epithelium
Standard
Intrachoroidal neovascularization in transgenic mice overexpressing vascular endothelial growth factor in the retinal pigment epithelium. / Meyer-Schwesinger, Catherine; Yee, C; Rohan, R M; Joussen, A M; Fernandez, A; Meyer, T N; Poulaki, V; Ma, J J; Redmond, T M; Liu, S; Adamis, A P; D'Amato, R J.
in: AM J PATHOL, Jahrgang 158, Nr. 3, 01.03.2001, S. 1161-72.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Intrachoroidal neovascularization in transgenic mice overexpressing vascular endothelial growth factor in the retinal pigment epithelium
AU - Meyer-Schwesinger, Catherine
AU - Yee, C
AU - Rohan, R M
AU - Joussen, A M
AU - Fernandez, A
AU - Meyer, T N
AU - Poulaki, V
AU - Ma, J J
AU - Redmond, T M
AU - Liu, S
AU - Adamis, A P
AU - D'Amato, R J
PY - 2001/3/1
Y1 - 2001/3/1
N2 - Choroidal neovascularization in age-related macular degeneration is a frequent and poorly treatable cause of vision loss in elderly Caucasians. This choroidal neovascularization has been associated with the expression of vascular endothelial growth factor (VEGF). In current animal models choroidal neovascularization is induced by subretinal injection of growth factors or vectors encoding growth factors such as VEGF, or by disruption of the Bruch's membrane/retinal pigment epithelium complex with laser treatment. We wished to establish a transgenic murine model of age-related macular degeneration, in which the overexpression of VEGF by the retinal pigment epithelium induces choroidal neovascularization. A construct consisting of a tissue-specific murine retinal pigment epithelium promoter (RPE(65) promoter) coupled to murine VEGF(164) cDNA with a rabbit beta-globin-3' UTR was introduced into the genome of albino mice. Transgene mRNA was expressed in the retinal pigment epithelium at all ages peaking at 4 months. The expression of VEGF protein was increased in both the retinal pigment epithelium and choroid. An increase of intravascular adherent leukocytes and vessel leakage was observed. Histopathology revealed intrachoroidal neovascularization that did not penetrate through an intact Bruch's membrane. These results support the hypothesis that additional insults to the integrity of Bruch's membrane are required to induce growth of choroidal vessels into the subretinal space as seen in age-related macular degeneration. This model may be useful to screen for inhibitors of choroidal vessel growth.
AB - Choroidal neovascularization in age-related macular degeneration is a frequent and poorly treatable cause of vision loss in elderly Caucasians. This choroidal neovascularization has been associated with the expression of vascular endothelial growth factor (VEGF). In current animal models choroidal neovascularization is induced by subretinal injection of growth factors or vectors encoding growth factors such as VEGF, or by disruption of the Bruch's membrane/retinal pigment epithelium complex with laser treatment. We wished to establish a transgenic murine model of age-related macular degeneration, in which the overexpression of VEGF by the retinal pigment epithelium induces choroidal neovascularization. A construct consisting of a tissue-specific murine retinal pigment epithelium promoter (RPE(65) promoter) coupled to murine VEGF(164) cDNA with a rabbit beta-globin-3' UTR was introduced into the genome of albino mice. Transgene mRNA was expressed in the retinal pigment epithelium at all ages peaking at 4 months. The expression of VEGF protein was increased in both the retinal pigment epithelium and choroid. An increase of intravascular adherent leukocytes and vessel leakage was observed. Histopathology revealed intrachoroidal neovascularization that did not penetrate through an intact Bruch's membrane. These results support the hypothesis that additional insults to the integrity of Bruch's membrane are required to induce growth of choroidal vessels into the subretinal space as seen in age-related macular degeneration. This model may be useful to screen for inhibitors of choroidal vessel growth.
KW - Age Factors
KW - Animals
KW - Bromodeoxyuridine
KW - Capillary Permeability
KW - Cell Adhesion
KW - Cell Division
KW - Choroid
KW - Coloring Agents
KW - Disease Models, Animal
KW - Endothelial Growth Factors
KW - Evans Blue
KW - Leukocytes
KW - Lymphokines
KW - Macular Degeneration
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Transgenic
KW - Neovascularization, Pathologic
KW - Pigment Epithelium of Eye
KW - Protein Biosynthesis
KW - Transcription, Genetic
KW - Transgenes
KW - Vascular Endothelial Growth Factor A
KW - Vascular Endothelial Growth Factors
U2 - 10.1016/S0002-9440(10)64063-1
DO - 10.1016/S0002-9440(10)64063-1
M3 - SCORING: Journal article
C2 - 11238064
VL - 158
SP - 1161
EP - 1172
JO - AM J PATHOL
JF - AM J PATHOL
SN - 0002-9440
IS - 3
ER -