Microphthalmia, persistent hyperplastic hyaloid vasculature and lens anomalies following overexpression of VEGF-A(188) from the alpha A-crystallin promoter

Catrin S. Rutland, Christopher Mitchell, Muneeb Nasir, Moritz A. Konerding, Hannes C. A. Drexler

Research output: Contribution to journalArticle

Abstract

PURPOSE: During growth of the embryonic eye, dose- and site-specific expression of heparin-binding growth factors is critical for the formation of an appropriate vascular supply. Overexpression of vascular endothelial growth factor-A(188) (VEGF-A(188)), a strongly heparin-binding, endothelial-specific mitogen, leads to severe disturbance of vascular and overall ocular morphology. This study aimed to evaluate the effects of VEGF-A(188) overexpression on growth of ocular tissue components. METHODS: Stereological and immunohistochemical methods were employed to identify the vascular profiles, ocular tissue proportions, and cell types in VEGF-A(188) transgenic mice and compare them with wild-type mice. RESULTS: In VEGF-A(188) transgenic mice, both lens tissue and total ocular volume were reduced, whereas cross-sectional areas of hyaloid blood vessels, retina, iris, and optic stalk tissues were significantly increased compared to wild-type mice. Endothelial and pericyte cell numbers in the hyaloid vasculature of transgenic mice were increased three fold, with pericytes assuming their characteristic extraluminal position. CONCLUSIONS: Overexpression of VEGF-A(188) in the murine lens results in microphthalmia, in addition to hypertrophy and persistence of the hyaloid vasculature. This is similar to the human disorder persistent hyperplastic primary vitreous (PHPV). The murine model is a useful, experimental paradigm for investigation of this condition.
LanguageEnglish
Pages47-56
JournalMOLECULAR VISION
Volume13
Issue number6
Publication statusPublished - Jan 2007

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alpha-Crystallin A Chain
Persistent Hyperplastic Primary Vitreous
Microphthalmos
Vascular Endothelial Growth Factor A
Lenses
Blood Vessels
Transgenic Mice
Pericytes
Heparin
Iris
Growth
Mitogens
Hypertrophy
Retina
Intercellular Signaling Peptides and Proteins
Endothelial Cells
Cell Count

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@article{3e095dc6e05542f48618aad9f8bf27cb,
title = "Microphthalmia, persistent hyperplastic hyaloid vasculature and lens anomalies following overexpression of VEGF-A(188) from the alpha A-crystallin promoter",
abstract = "PURPOSE: During growth of the embryonic eye, dose- and site-specific expression of heparin-binding growth factors is critical for the formation of an appropriate vascular supply. Overexpression of vascular endothelial growth factor-A(188) (VEGF-A(188)), a strongly heparin-binding, endothelial-specific mitogen, leads to severe disturbance of vascular and overall ocular morphology. This study aimed to evaluate the effects of VEGF-A(188) overexpression on growth of ocular tissue components. METHODS: Stereological and immunohistochemical methods were employed to identify the vascular profiles, ocular tissue proportions, and cell types in VEGF-A(188) transgenic mice and compare them with wild-type mice. RESULTS: In VEGF-A(188) transgenic mice, both lens tissue and total ocular volume were reduced, whereas cross-sectional areas of hyaloid blood vessels, retina, iris, and optic stalk tissues were significantly increased compared to wild-type mice. Endothelial and pericyte cell numbers in the hyaloid vasculature of transgenic mice were increased three fold, with pericytes assuming their characteristic extraluminal position. CONCLUSIONS: Overexpression of VEGF-A(188) in the murine lens results in microphthalmia, in addition to hypertrophy and persistence of the hyaloid vasculature. This is similar to the human disorder persistent hyperplastic primary vitreous (PHPV). The murine model is a useful, experimental paradigm for investigation of this condition.",
author = "Rutland, {Catrin S.} and Christopher Mitchell and Muneeb Nasir and Konerding, {Moritz A.} and Drexler, {Hannes C. A.}",
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Microphthalmia, persistent hyperplastic hyaloid vasculature and lens anomalies following overexpression of VEGF-A(188) from the alpha A-crystallin promoter. / Rutland, Catrin S.; Mitchell, Christopher; Nasir, Muneeb; Konerding, Moritz A.; Drexler, Hannes C. A.

Vol. 13, No. 6, 01.2007, p. 47-56.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Microphthalmia, persistent hyperplastic hyaloid vasculature and lens anomalies following overexpression of VEGF-A(188) from the alpha A-crystallin promoter

AU - Rutland, Catrin S.

AU - Mitchell, Christopher

AU - Nasir, Muneeb

AU - Konerding, Moritz A.

AU - Drexler, Hannes C. A.

PY - 2007/1

Y1 - 2007/1

N2 - PURPOSE: During growth of the embryonic eye, dose- and site-specific expression of heparin-binding growth factors is critical for the formation of an appropriate vascular supply. Overexpression of vascular endothelial growth factor-A(188) (VEGF-A(188)), a strongly heparin-binding, endothelial-specific mitogen, leads to severe disturbance of vascular and overall ocular morphology. This study aimed to evaluate the effects of VEGF-A(188) overexpression on growth of ocular tissue components. METHODS: Stereological and immunohistochemical methods were employed to identify the vascular profiles, ocular tissue proportions, and cell types in VEGF-A(188) transgenic mice and compare them with wild-type mice. RESULTS: In VEGF-A(188) transgenic mice, both lens tissue and total ocular volume were reduced, whereas cross-sectional areas of hyaloid blood vessels, retina, iris, and optic stalk tissues were significantly increased compared to wild-type mice. Endothelial and pericyte cell numbers in the hyaloid vasculature of transgenic mice were increased three fold, with pericytes assuming their characteristic extraluminal position. CONCLUSIONS: Overexpression of VEGF-A(188) in the murine lens results in microphthalmia, in addition to hypertrophy and persistence of the hyaloid vasculature. This is similar to the human disorder persistent hyperplastic primary vitreous (PHPV). The murine model is a useful, experimental paradigm for investigation of this condition.

AB - PURPOSE: During growth of the embryonic eye, dose- and site-specific expression of heparin-binding growth factors is critical for the formation of an appropriate vascular supply. Overexpression of vascular endothelial growth factor-A(188) (VEGF-A(188)), a strongly heparin-binding, endothelial-specific mitogen, leads to severe disturbance of vascular and overall ocular morphology. This study aimed to evaluate the effects of VEGF-A(188) overexpression on growth of ocular tissue components. METHODS: Stereological and immunohistochemical methods were employed to identify the vascular profiles, ocular tissue proportions, and cell types in VEGF-A(188) transgenic mice and compare them with wild-type mice. RESULTS: In VEGF-A(188) transgenic mice, both lens tissue and total ocular volume were reduced, whereas cross-sectional areas of hyaloid blood vessels, retina, iris, and optic stalk tissues were significantly increased compared to wild-type mice. Endothelial and pericyte cell numbers in the hyaloid vasculature of transgenic mice were increased three fold, with pericytes assuming their characteristic extraluminal position. CONCLUSIONS: Overexpression of VEGF-A(188) in the murine lens results in microphthalmia, in addition to hypertrophy and persistence of the hyaloid vasculature. This is similar to the human disorder persistent hyperplastic primary vitreous (PHPV). The murine model is a useful, experimental paradigm for investigation of this condition.

M3 - Article

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