title: Vitreous levels of placental growth factor correlate with activity of proliferative diabetic retinopathy and are not influenced by bevacizumab treatment.
abstract: PurposePlacental growth factor (PlGF) is a member of the VEGF family that plays an important role in experimental models of diabetic retinopathy and retinal neovascularization. We aimed to investigate whether vitreous levels of PlGF correlated with proliferative diabetic retinopathy (PDR) status, VEGF levels, and bevacizumab treatment. We also analysed PDR membranes to confirm the presence of the PlGF receptor, FLT1, in endothelial cells.MethodsThis was a case-control study: undiluted vitreous fluid samples were obtained from 28 active PDR patients without preoperative bevacizumab treatment, 21 active PDR patients with preoperative bevacizumab treatment, 18 inactive PDR patients, and 21 control patients. PlGF and VEGF levels in samples were determined by enzyme-linked immunosorbent assay. Immunohistochemistry for FLT1 was performed on human PDR membranes.ResultsCompared to control, vitreous PlGF levels were higher in both active PDR without bevacizumab (P<0.0001) and with bevacizumab (P<0.0001). There was no significant difference in PlGF between active PDR patients without and with bevacizumab (P=0.56). Compared to active PDR, PlGF levels were significantly reduced in inactive PDR (P=0.004). PlGF levels were highly correlated with VEGF levels in active PDR. VEGFR1 was expressed in endothelial cells in human PDR membranes.ConclusionThe strong correlation of PlGF levels with PDR disease status and expression of FLT1 in human PDR membranes suggest that PlGF has a pathogenic role in proliferative diabetic retinopathy. Therapeutic targeting of PlGF with agents like aflibercept may be beneficial.
authors.affiliation: King Khaled Eye Specialist Hospital, Riyadh, Kingdom of Saudi Arabia.
authors.forename: E
authors.initials: E
authors.lastname: Al Kahtani
authors.affiliation: Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Xu
authors.affiliation: King Khaled Eye Specialist Hospital, Riyadh, Kingdom of Saudi Arabia.
authors.forename: S
authors.initials: S
authors.lastname: Al Rashaed
authors.affiliation: Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: L
authors.initials: L
authors.lastname: Wu
authors.affiliation: King Khaled Eye Specialist Hospital, Riyadh, Kingdom of Saudi Arabia.
authors.forename: A
authors.initials: A
authors.lastname: Mahale
authors.affiliation: Department of Biostatistics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: J
authors.initials: J
authors.lastname: Tian
authors.affiliation: King Khaled Eye Specialist Hospital, Riyadh, Kingdom of Saudi Arabia.
authors.forename: E B
authors.initials: EB
authors.lastname: Abboud
authors.affiliation: King Khaled Eye Specialist Hospital, Riyadh, Kingdom of Saudi Arabia.
authors.forename: N G
authors.initials: NG
authors.lastname: Ghazi
authors.affiliation: King Khaled Eye Specialist Hospital, Riyadh, Kingdom of Saudi Arabia.
authors.forename: I
authors.initials: I
authors.lastname: Kozak
authors.affiliation: King Khaled Eye Specialist Hospital, Riyadh, Kingdom of Saudi Arabia.
authors.forename: V
authors.initials: V
authors.lastname: Gupta
authors.affiliation: King Khaled Eye Specialist Hospital, Riyadh, Kingdom of Saudi Arabia.|Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: J F
authors.initials: JF
authors.lastname: Arevalo
authors.affiliation: Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: E J
authors.initials: EJ
authors.lastname: Duh
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D003930:Diabetic Retinopathy / Q000188:drug therapy* / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007150:Immunohistochemistry; D000072483:Placenta Growth Factor / Q000378:metabolism*; D015861:Retinal Neovascularization / Q000473:pathology* / Q000601:surgery; D012529:Saudi Arabia; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism; D014821:Vitrectomy; D014822:Vitreous Body / Q000378:metabolism* / Q000473:pathology
chemical_list: D020533:Angiogenesis Inhibitors; D015415:Biomarkers; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000072483:Placenta Growth Factor; D000068258:Bevacizumab; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1