Qi Zhang1, Yun Qi1, Li Chen2, Xuan Shi1, Yujing Bai1, Lvzhen Huang1, Wenzhen Yu1, Yanrong Jiang1, Mingwei Zhao1, Xiaoxin Li1. 1. 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. 2. 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.
Abstract
PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
PURPOSE: 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. METHODS: 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. RESULTS: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. CONCLUSIONS: 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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
Authors: Rishika Chaudhary; Robert A H Scott; Graham Wallace; Martin Berry; Ann Logan; Richard J Blanch Journal: Transl Vis Sci Technol Date: 2020-02-21 Impact factor: 3.283
Authors: Mael Lever; Christian Halfwassen; Jan Darius Unterlauft; Nikolaos E Bechrakis; Anke Manthey; Michael R R Böhm Journal: Biology (Basel) Date: 2021-03-25