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Cellular stress response in human Müller cells (MIO-M1) after bevacizumab treatment.
Matsuda, Monique; Krempel, Paloma Gava; Marquezini, Mônica Valeria; Sholl-Franco, Alfred; Lameu, Amanda; Monteiro, Mário Luiz R; Miguel, Nádia Campos de Oliveira.
Afiliação
  • Matsuda M; Laboratory of Investigation in Ophthalmology (LIM-33), Division of Ophthalmology, University of São Paulo Medical School, Brazil.
  • Krempel PG; Laboratory of Investigation in Ophthalmology (LIM-33), Division of Ophthalmology, University of São Paulo Medical School, Brazil.
  • Marquezini MV; Laboratory of Experimental Air Pollution, University of São Paulo Medical School & Pro-Sangue Foundation, São Paulo, Brazil.
  • Sholl-Franco A; Laboratório de Neurogênese, Programa de Neurobiologia, Instituto de Biofísica Carlos Chagas Filho, UFRJ, Rio de Janeiro, Brazil.
  • Lameu A; Pharmacy College, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil.
  • Monteiro MLR; Laboratory of Investigation in Ophthalmology (LIM-33), Division of Ophthalmology, University of São Paulo Medical School, Brazil. Electronic address: mlrmonteiro@terra.com.br.
  • Miguel NCO; Program of Cell and Developmental Biology, Institute of Biomedical Sciences, Federal University of Rio de Janeiro (UFRJ), Brazil.
Exp Eye Res ; 160: 1-10, 2017 07.
Article em En | MEDLINE | ID: mdl-28419863
Bevacizumab, an anti-vascular endothelial growth factor (VEGF) agent, is widely used in the treatment of retinal vascular diseases. However, due to the essential role Müller cell derived-VEGF plays in the maintenance of retinal neurons and glial cells, cell viability is likely to be affected by VEGF inhibition. We therefore evaluated the effect of bevacizumab-induced VEGF inhibition on Müller cells (MIO-M1) in vitro. MIO-M1 cells were cultured for 12 or 24 h in media containing bevacizumab at 0.25 or 0.5 mg/mL. Controls were cultured in medium only. Cell viability was determined with the trypan blue exclusion test and MTT assay. Caspase-3, beclin-1, glial fibrillary acidic protein (GFAP) and vimentin content were quantified by immunohistochemistry. Gene expression was evaluated by real-time quantitative PCR. Treatment with bevacizumab did not reduce MIO-M1 cell viability, but increased metabolic activity at 24 h (0.5 mg/mL) and induced apoptosis and autophagy, as shown by the increased caspase-3 levels at 12 h (0.25 and 0.5 mg/mL) and the increased beclin levels at 24 h (0.5 mg/mL). Caspase-3 mRNA was upregulated at 12 h and downregulated at 24 h in cells treated with bevacizumab at 0.25 mg/mL. Bevacizumab treatment was also associated with structural protein abnormalities, with decreased GFAP and vimentin content and upregulated GFAP and vimentin mRNA expression. Although bevacizumab did not significantly affect MIO-M1 cell viability, it led to metabolic and molecular changes (apoptosis, autophagy and structural abnormalities) suggestive of significant cellular toxicity.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Vimentina / RNA / Regulação da Expressão Gênica / Células Ependimogliais / Bevacizumab / Proteína Glial Fibrilar Ácida Limite: Humans Idioma: En Revista: Exp Eye Res Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Brasil País de publicação: Reino Unido
Texto completo
Adicionar na Minha BVS
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XML
PubMed Links
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Vimentina / RNA / Regulação da Expressão Gênica / Células Ependimogliais / Bevacizumab / Proteína Glial Fibrilar Ácida Limite: Humans Idioma: En Revista: Exp Eye Res Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Brasil País de publicação: Reino Unido