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Acta Ophthalmol. 2018 Feb;96(1):e1-e9. doi: 10.1111/aos.13325. Epub 2016 Nov 22.

Placental growth factor and its potential role in diabetic retinopathy and other ocular neovascular diseases.

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Ocular Imaging Research and Reading Center, Omaha, Nebraska, USA.
Angiogenesis Laboratory, Institute of Genetics and Biophysics-CNR, Naples, Italy.
INSERM U1138, UMR_S 1138, Research Center of Cordeliers, Paris Descartes University, UPMC University, Sorbonne Paris Cité, Paris, France.
Department of Ophthalmology of University of Lausanne, Jules Gonin Hospital, Asylum Foundation for the Blind, Lausanne, Switzerland.
Department of Ophthalmology, University of Toronto, Toronto, Ontario, Canada.
State Key Laboratory of Ophthalmology, Sun-Yat Sen University, Guangzhou, China.
Experimental Ophthalmology, Eye Clinic, Charité Medical University, Berlin, Germany.
UOSD Retinal Diseases Foundation PTV 'Polyclinic Tor Vergata', Rome, Italy.
Bayer Pharmaceuticals, Whippany, New Jersey, USA.
The Angiogenesis Foundation, Cambridge, Massachusetts, USA.


The role of vascular endothelial growth factor (VEGF), including in retinal vascular diseases, has been well studied, and pharmacological blockade of VEGF is the gold standard of treatment for neovascular age-related macular degeneration, retinal vein occlusion and diabetic macular oedema. Placental growth factor (PGF, previously known as PlGF), a homologue of VEGF, is a multifunctional peptide associated with angiogenesis-dependent pathologies in the eye and non-ocular conditions. Animal studies using genetic modification and pharmacological treatment have demonstrated a mechanistic role for PGF in pathological angiogenesis. Inhibition decreases neovascularization and microvascular abnormalities across different models, including oxygen-induced retinopathy, laser-induced choroidal neovascularization and in diabetic mice exhibiting retinopathies. High levels of PGF have been found in the vitreous of patients with diabetic retinopathy. Despite these strong animal data, the exact role of PGF in pathological angiogenesis in retinal vascular diseases remains to be defined, and the benefits of PGF-specific inhibition in humans with retinal neovascular diseases and macular oedema remain controversial. Comparative effectiveness research studies in patients with diabetic retinal disease have shown that treatment that inhibits both VEGF and PGF may provide superior outcomes in certain patients compared with treatment that inhibits only VEGF. This review summarizes current knowledge of PGF, including its relationship to VEGF and its role in pathological angiogenesis in retinal diseases, and identifies some key unanswered questions about PGF that can serve as a pathway for future basic, translational and clinical research.


angiogenesis; diabetic retinopathy; neovascularization; placental growth factor; retina; vascular endothelial growth factor

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