Differences in the temporal expression of regulatory growth factors during choroidal neovascular development

Wenzheng Hu, Mark H. Criswell, Shao Ling Fong, Constance J. Temm, Gangaraju Rajashekhar, Tammy L. Cornell, Matthias Clauss

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Although the roles of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and hepatocyte growth factor (HGF) in pathologic neovascularization have been well characterized in certain tissues, their particular functions and expression patterns in choroidal neovascularization (CNV) have not been clearly established. After localized laser trauma to Bruch's membrane to induce CNV development, the temporal changes in mRNA and protein expression of these 3 cytokines were documented and compared histologically to areas of immunofluorescence, the proliferation of endothelial cells, neovascular development, and temporal changes in vascular permeability. Changes in mRNA and protein levels of bFGF and HGF occurred quickly and reached peak expression within hours. This activity corresponded in time to intense and localized immunofluorescence for these cytokines within the choriocapillaris within laser lesion sites. During this same initial time period, mRNA upregulation of VEGF occurred, primarily within the neural retina and this expression corresponded to intense immunolabeling of Müller cells immediately adjacent to the lesion sites. By 3 days after lasering, increased VEGF164 protein expression was measurable, whereas early neovascular development histologically corresponded to HGF and bFGF mRNA expansion into the developing choroidal neovascular membrane (CNVM). At 7 days, CNV expansion, maturation, and increased vascular permeability corresponded to peak VEGF mRNA and protein expression and to immunofluorescence of the CNVM. Differences also occurred in the expression of precursor and activated isoforms of these cytokines in the retinal pigment epithelium/choroid as compared to those in the retina. These molecular and immunocytochemical results suggest that bFGF and HGF may be important as initial regulators neovascularization in this CNV model; whereas VEGF may be important during later phases of angiogenesis and neovascular hyperpermeability.

Original languageEnglish
Pages (from-to)79-91
Number of pages13
JournalExperimental Eye Research
Volume88
Issue number1
DOIs
StatePublished - Jan 5 2009

Fingerprint

Choroidal Neovascularization
Hepatocyte Growth Factor
Fibroblast Growth Factor 2
Intercellular Signaling Peptides and Proteins
Vascular Endothelial Growth Factor A
Messenger RNA
Fluorescent Antibody Technique
Capillary Permeability
Cytokines
Retina
Proteins
Lasers
Pathologic Neovascularization
Bruch Membrane
Membranes
Choroid
Retinal Pigment Epithelium
Protein Isoforms
Up-Regulation
Endothelial Cells

Keywords

  • anastomoses
  • angiogenesis
  • basic fibroblast growth factor
  • choroidal neovascularization
  • hepatocyte growth factor
  • laser photocoagulation
  • neovascular hyperpermeability
  • vascular endothelial growth factor

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Differences in the temporal expression of regulatory growth factors during choroidal neovascular development. / Hu, Wenzheng; Criswell, Mark H.; Fong, Shao Ling; Temm, Constance J.; Rajashekhar, Gangaraju; Cornell, Tammy L.; Clauss, Matthias.

In: Experimental Eye Research, Vol. 88, No. 1, 05.01.2009, p. 79-91.

Research output: Contribution to journalArticle

Hu, Wenzheng ; Criswell, Mark H. ; Fong, Shao Ling ; Temm, Constance J. ; Rajashekhar, Gangaraju ; Cornell, Tammy L. ; Clauss, Matthias. / Differences in the temporal expression of regulatory growth factors during choroidal neovascular development. In: Experimental Eye Research. 2009 ; Vol. 88, No. 1. pp. 79-91.
@article{bb35ae1163dd45d4befbc0bb6ea7b3ad,
title = "Differences in the temporal expression of regulatory growth factors during choroidal neovascular development",
abstract = "Although the roles of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and hepatocyte growth factor (HGF) in pathologic neovascularization have been well characterized in certain tissues, their particular functions and expression patterns in choroidal neovascularization (CNV) have not been clearly established. After localized laser trauma to Bruch's membrane to induce CNV development, the temporal changes in mRNA and protein expression of these 3 cytokines were documented and compared histologically to areas of immunofluorescence, the proliferation of endothelial cells, neovascular development, and temporal changes in vascular permeability. Changes in mRNA and protein levels of bFGF and HGF occurred quickly and reached peak expression within hours. This activity corresponded in time to intense and localized immunofluorescence for these cytokines within the choriocapillaris within laser lesion sites. During this same initial time period, mRNA upregulation of VEGF occurred, primarily within the neural retina and this expression corresponded to intense immunolabeling of M{\"u}ller cells immediately adjacent to the lesion sites. By 3 days after lasering, increased VEGF164 protein expression was measurable, whereas early neovascular development histologically corresponded to HGF and bFGF mRNA expansion into the developing choroidal neovascular membrane (CNVM). At 7 days, CNV expansion, maturation, and increased vascular permeability corresponded to peak VEGF mRNA and protein expression and to immunofluorescence of the CNVM. Differences also occurred in the expression of precursor and activated isoforms of these cytokines in the retinal pigment epithelium/choroid as compared to those in the retina. These molecular and immunocytochemical results suggest that bFGF and HGF may be important as initial regulators neovascularization in this CNV model; whereas VEGF may be important during later phases of angiogenesis and neovascular hyperpermeability.",
keywords = "anastomoses, angiogenesis, basic fibroblast growth factor, choroidal neovascularization, hepatocyte growth factor, laser photocoagulation, neovascular hyperpermeability, vascular endothelial growth factor",
author = "Wenzheng Hu and Criswell, {Mark H.} and Fong, {Shao Ling} and Temm, {Constance J.} and Gangaraju Rajashekhar and Cornell, {Tammy L.} and Matthias Clauss",
year = "2009",
month = "1",
day = "5",
doi = "10.1016/j.exer.2008.10.014",
language = "English",
volume = "88",
pages = "79--91",
journal = "Experimental Eye Research",
issn = "0014-4835",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - Differences in the temporal expression of regulatory growth factors during choroidal neovascular development

AU - Hu, Wenzheng

AU - Criswell, Mark H.

AU - Fong, Shao Ling

AU - Temm, Constance J.

AU - Rajashekhar, Gangaraju

AU - Cornell, Tammy L.

AU - Clauss, Matthias

PY - 2009/1/5

Y1 - 2009/1/5

N2 - Although the roles of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and hepatocyte growth factor (HGF) in pathologic neovascularization have been well characterized in certain tissues, their particular functions and expression patterns in choroidal neovascularization (CNV) have not been clearly established. After localized laser trauma to Bruch's membrane to induce CNV development, the temporal changes in mRNA and protein expression of these 3 cytokines were documented and compared histologically to areas of immunofluorescence, the proliferation of endothelial cells, neovascular development, and temporal changes in vascular permeability. Changes in mRNA and protein levels of bFGF and HGF occurred quickly and reached peak expression within hours. This activity corresponded in time to intense and localized immunofluorescence for these cytokines within the choriocapillaris within laser lesion sites. During this same initial time period, mRNA upregulation of VEGF occurred, primarily within the neural retina and this expression corresponded to intense immunolabeling of Müller cells immediately adjacent to the lesion sites. By 3 days after lasering, increased VEGF164 protein expression was measurable, whereas early neovascular development histologically corresponded to HGF and bFGF mRNA expansion into the developing choroidal neovascular membrane (CNVM). At 7 days, CNV expansion, maturation, and increased vascular permeability corresponded to peak VEGF mRNA and protein expression and to immunofluorescence of the CNVM. Differences also occurred in the expression of precursor and activated isoforms of these cytokines in the retinal pigment epithelium/choroid as compared to those in the retina. These molecular and immunocytochemical results suggest that bFGF and HGF may be important as initial regulators neovascularization in this CNV model; whereas VEGF may be important during later phases of angiogenesis and neovascular hyperpermeability.

AB - Although the roles of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and hepatocyte growth factor (HGF) in pathologic neovascularization have been well characterized in certain tissues, their particular functions and expression patterns in choroidal neovascularization (CNV) have not been clearly established. After localized laser trauma to Bruch's membrane to induce CNV development, the temporal changes in mRNA and protein expression of these 3 cytokines were documented and compared histologically to areas of immunofluorescence, the proliferation of endothelial cells, neovascular development, and temporal changes in vascular permeability. Changes in mRNA and protein levels of bFGF and HGF occurred quickly and reached peak expression within hours. This activity corresponded in time to intense and localized immunofluorescence for these cytokines within the choriocapillaris within laser lesion sites. During this same initial time period, mRNA upregulation of VEGF occurred, primarily within the neural retina and this expression corresponded to intense immunolabeling of Müller cells immediately adjacent to the lesion sites. By 3 days after lasering, increased VEGF164 protein expression was measurable, whereas early neovascular development histologically corresponded to HGF and bFGF mRNA expansion into the developing choroidal neovascular membrane (CNVM). At 7 days, CNV expansion, maturation, and increased vascular permeability corresponded to peak VEGF mRNA and protein expression and to immunofluorescence of the CNVM. Differences also occurred in the expression of precursor and activated isoforms of these cytokines in the retinal pigment epithelium/choroid as compared to those in the retina. These molecular and immunocytochemical results suggest that bFGF and HGF may be important as initial regulators neovascularization in this CNV model; whereas VEGF may be important during later phases of angiogenesis and neovascular hyperpermeability.

KW - anastomoses

KW - angiogenesis

KW - basic fibroblast growth factor

KW - choroidal neovascularization

KW - hepatocyte growth factor

KW - laser photocoagulation

KW - neovascular hyperpermeability

KW - vascular endothelial growth factor

UR - http://www.scopus.com/inward/record.url?scp=57549097985&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=57549097985&partnerID=8YFLogxK

U2 - 10.1016/j.exer.2008.10.014

DO - 10.1016/j.exer.2008.10.014

M3 - Article

VL - 88

SP - 79

EP - 91

JO - Experimental Eye Research

JF - Experimental Eye Research

SN - 0014-4835

IS - 1

ER -