The role of placental growth factor (PlGF) and its receptor system in retinal vascular diseases

Tine Van Bergen, Isabelle Etienne, Fiona Cunningham, Lieve Moons, Reinier O. Schlingemann, Jean H.M. Feyen, Alan W. Stitt*

*Corresponding author for this work

Research output: Contribution to journalReview article

4 Citations (Scopus)

Abstract

Placental growth factor (PlGF) is a member of the vascular endothelial growth factor (VEGF) family. Upon binding to VEGF- and neuropilin-receptor sub-types, PlGF modulates a range of neural, glial and vascular cell responses that are distinct from VEGF-A. As PlGF expression is selectively associated with pathological angiogenesis and inflammation, its blockade does not affect the healthy vasculature. PlGF actions have been extensively described in tumor biology but more recently there has been accumulating preclinical evidence that indicates that this growth factor could have an important role in retinal diseases. High levels of PlGF have been found in aqueous humor, vitreous and/or retina of patients exhibiting retinopathies, especially those with diabetic retinopathy (DR) and neovascular age-related macular degeneration (nvAMD). Expression of this growth factor seems to correlate closely with many of the key pathogenic features of early and late retinopathy in preclinical models. For example, studies using genetic modification and/or pharmacological treatment to block PlGF in the laser-induced choroidal neovascularization (CNV) model, oxygen-induced retinopathy model, as well as various murine diabetic models, have shown that PlGF deletion or inhibition can reduce neovascularization, retinal leakage, inflammation and gliosis, without affecting vascular development or inducing neuronal degeneration. Moreover, an inhibitory effect of PlGF blockade on retinal scarring in the mouse CNV model has also been recently demonstrated and was found to be unique for PlGF inhibition, as compared to various VEGF inhibition strategies. Together, these preclinical results suggest that anti-PlGF therapy might have advantages over anti-VEGF treatment, and that it may have clinical applications as a standalone treatment or in combination with anti-VEGF. Additional clinical studies are clearly needed to further elucidate the role of PlGF and its potential as a therapeutic target in ocular diseases.

Original languageEnglish
Pages (from-to)116-136
Number of pages21
JournalProgress in Retinal and Eye Research
Volume69
Early online date30 Oct 2018
DOIs
Publication statusPublished - 01 Mar 2019

Fingerprint

Retinal Diseases
Retinal Vessels
Growth Factor Receptors
Vascular Diseases
Intercellular Signaling Peptides and Proteins
Vascular Endothelial Growth Factor A
Choroidal Neovascularization
Blood Vessels
Neuropilins
Pathologic Neovascularization
Retinal Neovascularization
Inflammation
Therapeutics
Vascular Endothelial Growth Factor Receptor
Gliosis
Eye Diseases
Aqueous Humor
Macular Degeneration
Diabetic Retinopathy
Neuroglia

Keywords

  • Age-related macular degeneration
  • Diabetic retinopathy
  • Placental growth factor
  • Retinal diseases
  • VEGFR-1

Cite this

Van Bergen, Tine ; Etienne, Isabelle ; Cunningham, Fiona ; Moons, Lieve ; Schlingemann, Reinier O. ; Feyen, Jean H.M. ; Stitt, Alan W. / The role of placental growth factor (PlGF) and its receptor system in retinal vascular diseases. In: Progress in Retinal and Eye Research. 2019 ; Vol. 69. pp. 116-136.
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The role of placental growth factor (PlGF) and its receptor system in retinal vascular diseases. / Van Bergen, Tine; Etienne, Isabelle; Cunningham, Fiona; Moons, Lieve; Schlingemann, Reinier O.; Feyen, Jean H.M.; Stitt, Alan W.

In: Progress in Retinal and Eye Research, Vol. 69, 01.03.2019, p. 116-136.

Research output: Contribution to journalReview article

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T1 - The role of placental growth factor (PlGF) and its receptor system in retinal vascular diseases

AU - Van Bergen, Tine

AU - Etienne, Isabelle

AU - Cunningham, Fiona

AU - Moons, Lieve

AU - Schlingemann, Reinier O.

AU - Feyen, Jean H.M.

AU - Stitt, Alan W.

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N2 - Placental growth factor (PlGF) is a member of the vascular endothelial growth factor (VEGF) family. Upon binding to VEGF- and neuropilin-receptor sub-types, PlGF modulates a range of neural, glial and vascular cell responses that are distinct from VEGF-A. As PlGF expression is selectively associated with pathological angiogenesis and inflammation, its blockade does not affect the healthy vasculature. PlGF actions have been extensively described in tumor biology but more recently there has been accumulating preclinical evidence that indicates that this growth factor could have an important role in retinal diseases. High levels of PlGF have been found in aqueous humor, vitreous and/or retina of patients exhibiting retinopathies, especially those with diabetic retinopathy (DR) and neovascular age-related macular degeneration (nvAMD). Expression of this growth factor seems to correlate closely with many of the key pathogenic features of early and late retinopathy in preclinical models. For example, studies using genetic modification and/or pharmacological treatment to block PlGF in the laser-induced choroidal neovascularization (CNV) model, oxygen-induced retinopathy model, as well as various murine diabetic models, have shown that PlGF deletion or inhibition can reduce neovascularization, retinal leakage, inflammation and gliosis, without affecting vascular development or inducing neuronal degeneration. Moreover, an inhibitory effect of PlGF blockade on retinal scarring in the mouse CNV model has also been recently demonstrated and was found to be unique for PlGF inhibition, as compared to various VEGF inhibition strategies. Together, these preclinical results suggest that anti-PlGF therapy might have advantages over anti-VEGF treatment, and that it may have clinical applications as a standalone treatment or in combination with anti-VEGF. Additional clinical studies are clearly needed to further elucidate the role of PlGF and its potential as a therapeutic target in ocular diseases.

AB - Placental growth factor (PlGF) is a member of the vascular endothelial growth factor (VEGF) family. Upon binding to VEGF- and neuropilin-receptor sub-types, PlGF modulates a range of neural, glial and vascular cell responses that are distinct from VEGF-A. As PlGF expression is selectively associated with pathological angiogenesis and inflammation, its blockade does not affect the healthy vasculature. PlGF actions have been extensively described in tumor biology but more recently there has been accumulating preclinical evidence that indicates that this growth factor could have an important role in retinal diseases. High levels of PlGF have been found in aqueous humor, vitreous and/or retina of patients exhibiting retinopathies, especially those with diabetic retinopathy (DR) and neovascular age-related macular degeneration (nvAMD). Expression of this growth factor seems to correlate closely with many of the key pathogenic features of early and late retinopathy in preclinical models. For example, studies using genetic modification and/or pharmacological treatment to block PlGF in the laser-induced choroidal neovascularization (CNV) model, oxygen-induced retinopathy model, as well as various murine diabetic models, have shown that PlGF deletion or inhibition can reduce neovascularization, retinal leakage, inflammation and gliosis, without affecting vascular development or inducing neuronal degeneration. Moreover, an inhibitory effect of PlGF blockade on retinal scarring in the mouse CNV model has also been recently demonstrated and was found to be unique for PlGF inhibition, as compared to various VEGF inhibition strategies. Together, these preclinical results suggest that anti-PlGF therapy might have advantages over anti-VEGF treatment, and that it may have clinical applications as a standalone treatment or in combination with anti-VEGF. Additional clinical studies are clearly needed to further elucidate the role of PlGF and its potential as a therapeutic target in ocular diseases.

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KW - Diabetic retinopathy

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KW - Retinal diseases

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