title: Increased circulating PEDF and low sICAM-1 are associated with sickle cell retinopathy.
abstract: Sickle cell retinopathy (SCR) develops in up to 30% of sickle cell disease patients (SCD) during the second decade of life. Treatment for this affection remains palliative, so studies on its pathophysiology may contribute to the future development of novel therapies. SCR is more frequently observed in hemoglobin SC disease and derives from vaso-occlusion in the microvasculature of the retina leading to neovascularization and, eventually, to blindness. Circulating inflammatory cytokines, angiogenic factors, and their interaction may contribute to the pathophysiology of this complication. Angiopoietin (Ang)-1, Ang-2, soluble vascular cell adhesion molecule-1, intercellular adhesion molecule (ICAM)-1, E-selectin, P-selectin, IL1-β, TNF-α, pigment epithelium derived factor (PEDF) and vascular endothelial growth factor plasmatic levels were determined in 37 SCD patients with retinopathy, 34 without retinopathy, and healthy controls. We observed that sICAM-1 is significantly decreased, whereas PEDF is elevated in HbSC patients with retinopathy (P=0.012 and P=0.031, respectively). Ang-1, Ang-2 and IL1-β levels were elevated in SCD patients (P=0.001, P<0.001 and P=0.001, respectively), compared to controls, and HbSS patients presented higher levels of Ang-2 compared to HbSC (P<0.001). Our study supports the possible influence of sICAM-1 and PEDF on the pathophysiology of retinal neovascularization in SCD patients.
authors.affiliation: Laboratory of Human Molecular Genetics, Center of Molecular Biology and Genetic Engineering (CBMEG), University of Campinas-UNICAMP, Campinas, São Paulo, Brazil. Electronic address: soulsacross@gmail.com.
authors.forename: P R S
authors.initials: PR
authors.lastname: Cruz
authors.affiliation: Department of Ophthalmology, Faculty of Medical Sciences, University of Campinas-UNICAMP, Campinas, São Paulo, Brazil. Electronic address: rodrigopclira@hotmail.com.
authors.forename: R P C
authors.initials: RP
authors.lastname: Lira
authors.affiliation: Department of Ophthalmology, Faculty of Medical Sciences, University of Campinas-UNICAMP, Campinas, São Paulo, Brazil. Electronic address: sergioacpf@gmail.com.
authors.forename: S A C
authors.initials: SA
authors.lastname: Pereira Filho
authors.affiliation: Laboratory of Human Molecular Genetics, Center of Molecular Biology and Genetic Engineering (CBMEG), University of Campinas-UNICAMP, Campinas, São Paulo, Brazil. Electronic address: brunobsouzaa@gmail.com.
authors.forename: B B
authors.initials: BB
authors.lastname: Souza
authors.affiliation: Department of Ophthalmology, Faculty of Medical Sciences, University of Campinas-UNICAMP, Campinas, São Paulo, Brazil. Electronic address: fabionero@hotmail.com.
authors.forename: F N
authors.initials: FN
authors.lastname: Mitsuushi
authors.affiliation: Laboratory of Human Molecular Genetics, Center of Molecular Biology and Genetic Engineering (CBMEG), University of Campinas-UNICAMP, Campinas, São Paulo, Brazil. Electronic address: fmenaa@yahoo.com.
authors.forename: F
authors.initials: F
authors.lastname: Menaa
authors.affiliation: Hematology and Hemotherapy Center, University of Campinas, Campinas, São Paulo, Brazil. Electronic address: kleberfertrin@gmail.com.
authors.forename: K Y
authors.initials: KY
authors.lastname: Fertrin
authors.affiliation: Department of Ophthalmology, Faculty of Medical Sciences, University of Campinas-UNICAMP, Campinas, São Paulo, Brazil. Electronic address: cabraljp@uol.com.br.
authors.forename: J P C
authors.initials: JP
authors.lastname: Vasconcellos
authors.affiliation: Hematology and Hemotherapy Center, University of Campinas, Campinas, São Paulo, Brazil. Electronic address: conran@unicamp.br.
authors.forename: N
authors.initials: N
authors.lastname: Conran
authors.affiliation: Hematology and Hemotherapy Center, University of Campinas, Campinas, São Paulo, Brazil. Electronic address: ferreira@unicamp.br.
authors.forename: F F
authors.initials: FF
authors.lastname: Costa
authors.affiliation: Laboratory of Human Molecular Genetics, Center of Molecular Biology and Genetic Engineering (CBMEG), University of Campinas-UNICAMP, Campinas, São Paulo, Brazil. Electronic address: melomb@unicamp.br.
authors.forename: M B
authors.initials: MB
authors.lastname: Melo
mesh_terms: D000328:Adult; D000755:Anemia, Sickle Cell / Q000097:blood* / Q000150:complications; D042683:Angiopoietin-1 / Q000097:blood; D042702:Angiopoietin-2 / Q000097:blood; D016022:Case-Control Studies; D005136:Eye Proteins / Q000097:blood*; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood*; D053583:Interleukin-1beta / Q000097:blood; D008297:Male; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000097:blood*; D015861:Retinal Neovascularization / Q000097:blood* / Q000209:etiology; D015843:Serpins / Q000097:blood*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D042683:Angiopoietin-1; D042702:Angiopoietin-2; D005136:Eye Proteins; D018799:Intercellular Adhesion Molecule-1; D053583:Interleukin-1beta; D009414:Nerve Growth Factors; D015843:Serpins; D014409:Tumor Necrosis Factor-alpha; D000099174:Pigment Epithelium-Derived Factor; C467630:ANGPT1 protein, human; C586513:ANGPT2 protein, human; C573420:ICAM1 protein, human; C508585:IL1B protein, human
keywords: Adhesion molecules; Angiogenesis; Inflammation; Retinopathy; Sickle cell disease