title: The relationship between anti-vascular endothelial growth factor and fibrosis in proliferative retinopathy: clinical and laboratory evidence.
abstract: To investigate the progression of epiretinal membranes after intravitreal bevacizumab (IVB) injection therapy in patients with proliferative membranes and evaluate the changes in fibrosis-related cytokines in retinal pigment epithelial cells and glial cells after treatment with bevacizumab.
  
  
  
  Retrospective study of the proliferative membranes in patients with and without IVB therapy. In vitro, the human adult retinal pigment epithelial (ARPE-19) cells and BV2 microglial cell lines were incubated in different bevacizumab concentrations under hypoxic conditions. Cell culture supernatants and cell lysates were harvested after incubation for 24, 48 or 72 hours for ELISA and western blot.
  
  
  
  Bevacizumab accelerated fibrosis in patients with proliferative membranes. Immunofluorescence analysis revealed more intense transforming growth factor β2 (TGFβ2) and connective tissue growth factor (CTGF) staining in IVB-treated proliferative diabetic retinopathy (PDR) membranes compared with membranes of patients not receiving IVB therapy. This result was consistent with real-time PCR results. Bevacizumab incubation significantly upregulated TGFβ2 and CTGF in ARPE-19 cells and BV2 microglial cells, but ciliary neurotrophic factor (CNTF) expression was upregulated only in BV2 microglial cells.
  
  
  
  Anti-vascular endothelial growth factor treatment likely accelerates fibrosis in PDR patients via upregulation of TGFβ2, CTGF and CNTF, suggesting the importance of adjunctive therapy for retinal fibrosis.
authors.affiliation: Department of Ophthalmology, Peking University People's Hospital, Key Laboratory of Vision Loss and Restoration, Ministry of Education, Beijing, China Beijing Key Laboratory for the Diagnosis and Treatment of Retinal and Choroid Diseases, Beijing, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Ophthalmology, Peking University People's Hospital, Key Laboratory of Vision Loss and Restoration, Ministry of Education, Beijing, China Beijing Key Laboratory for the Diagnosis and Treatment of Retinal and Choroid Diseases, Beijing, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Qi
authors.affiliation: Department of Ophthalmology, Peking University People's Hospital, Key Laboratory of Vision Loss and Restoration, Ministry of Education, Beijing, China Beijing Key Laboratory for the Diagnosis and Treatment of Retinal and Choroid Diseases, Beijing, China Ophthalmology Department, Xian No. 4 Hospital, Xincheng District, Xi'an, China.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Ophthalmology, Peking University People's Hospital, Key Laboratory of Vision Loss and Restoration, Ministry of Education, Beijing, China Beijing Key Laboratory for the Diagnosis and Treatment of Retinal and Choroid Diseases, Beijing, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Shi
authors.affiliation: Department of Ophthalmology, Peking University People's Hospital, Key Laboratory of Vision Loss and Restoration, Ministry of Education, Beijing, China Beijing Key Laboratory for the Diagnosis and Treatment of Retinal and Choroid Diseases, Beijing, China.
authors.forename: Yujing
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Department of Ophthalmology, Peking University People's Hospital, Key Laboratory of Vision Loss and Restoration, Ministry of Education, Beijing, China Beijing Key Laboratory for the Diagnosis and Treatment of Retinal and Choroid Diseases, Beijing, China.
authors.forename: Lvzhen
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Ophthalmology, Peking University People's Hospital, Key Laboratory of Vision Loss and Restoration, Ministry of Education, Beijing, China Beijing Key Laboratory for the Diagnosis and Treatment of Retinal and Choroid Diseases, Beijing, China.
authors.forename: Wenzhen
authors.initials: W
authors.lastname: Yu
authors.affiliation: Department of Ophthalmology, Peking University People's Hospital, Key Laboratory of Vision Loss and Restoration, Ministry of Education, Beijing, China Beijing Key Laboratory for the Diagnosis and Treatment of Retinal and Choroid Diseases, Beijing, China.
authors.forename: Yanrong
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Ophthalmology, Peking University People's Hospital, Key Laboratory of Vision Loss and Restoration, Ministry of Education, Beijing, China Beijing Key Laboratory for the Diagnosis and Treatment of Retinal and Choroid Diseases, Beijing, China.
authors.forename: Mingwei
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Department of Ophthalmology, Peking University People's Hospital, Key Laboratory of Vision Loss and Restoration, Ministry of Education, Beijing, China Beijing Key Laboratory for the Diagnosis and Treatment of Retinal and Choroid Diseases, Beijing, China.
authors.forename: Xiaoxin
authors.initials: X
authors.lastname: Li
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D000068258:Bevacizumab / Q000008:administration & dosage*; D015153:Blotting, Western; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005355:Fibrosis; D005500:Follow-Up Studies; D005786:Gene Expression Regulation; D006801:Humans; D058449:Intravitreal Injections; D008297:Male; D008875:Middle Aged; D012313:RNA / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D013997:Time Factors; D053781:Transforming Growth Factor beta2 / Q000096:biosynthesis / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018630:Vitreoretinopathy, Proliferative / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D014822:Vitreous Body / Q000000981:diagnostic imaging* / Q000187:drug effects
chemical_list: D020533:Angiogenesis Inhibitors; D053781:Transforming Growth Factor beta2; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D012313:RNA
keywords: Drugs; Retina