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Intrachoroidal neovascularization in transgenic mice overexpressing vascular endothelial growth factor in the retinal pigment epithelium

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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, Vol. 158, No. 3, 01.03.2001, p. 1161-72.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Meyer-Schwesinger, C, Yee, C, Rohan, RM, Joussen, AM, Fernandez, A, Meyer, TN, Poulaki, V, Ma, JJ, Redmond, TM, Liu, S, Adamis, AP & D'Amato, RJ 2001, 'Intrachoroidal neovascularization in transgenic mice overexpressing vascular endothelial growth factor in the retinal pigment epithelium', AM J PATHOL, vol. 158, no. 3, pp. 1161-72. https://doi.org/10.1016/S0002-9440(10)64063-1

APA

Meyer-Schwesinger, C., 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. (2001). Intrachoroidal neovascularization in transgenic mice overexpressing vascular endothelial growth factor in the retinal pigment epithelium. AM J PATHOL, 158(3), 1161-72. https://doi.org/10.1016/S0002-9440(10)64063-1

Vancouver

Meyer-Schwesinger C, Yee C, Rohan RM, Joussen AM, Fernandez A, Meyer TN et al. Intrachoroidal neovascularization in transgenic mice overexpressing vascular endothelial growth factor in the retinal pigment epithelium. AM J PATHOL. 2001 Mar 1;158(3):1161-72. https://doi.org/10.1016/S0002-9440(10)64063-1

Bibtex

@article{36b989300af0470da4c108eecdac3894,
title = "Intrachoroidal neovascularization in transgenic mice overexpressing vascular endothelial growth factor in the retinal pigment epithelium",
abstract = "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.",
keywords = "Age Factors, Animals, Bromodeoxyuridine, Capillary Permeability, Cell Adhesion, Cell Division, Choroid, Coloring Agents, Disease Models, Animal, Endothelial Growth Factors, Evans Blue, Leukocytes, Lymphokines, Macular Degeneration, Mice, Mice, Inbred C57BL, Mice, Transgenic, Neovascularization, Pathologic, Pigment Epithelium of Eye, Protein Biosynthesis, Transcription, Genetic, Transgenes, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factors",
author = "Catherine Meyer-Schwesinger and C Yee and Rohan, {R M} and Joussen, {A M} and A Fernandez and Meyer, {T N} and V Poulaki and Ma, {J J} and Redmond, {T M} and S Liu and Adamis, {A P} and D'Amato, {R J}",
year = "2001",
month = mar,
day = "1",
doi = "10.1016/S0002-9440(10)64063-1",
language = "English",
volume = "158",
pages = "1161--72",
journal = "AM J PATHOL",
issn = "0002-9440",
publisher = "Elsevier Inc.",
number = "3",

}

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 -