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Immunohystochemical and gene expression analysis of the effect of bevacizumab upon lister rat retinal explants and on a human Müller glial cell line

Grant number: 11/12271-3
Support type:Regular Research Grants
Duration: October 01, 2011 - March 31, 2014
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Mário Luiz Ribeiro Monteiro
Grantee:Mário Luiz Ribeiro Monteiro
Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Assoc. researchers:Mônica Valeria Marquezini ; Monique Matsuda ; Nadia Campos de Oliveira Miguel


Retinal diseases that are associated to neovascularization, such as age-related macular degeneration, diabetic retinopathy and retinopathy of prematurity are important causes of blindness throughout the world. In the last years, intravitreal injection of anti-angiogenic drugs, such as bevacizumab, has been of great value both in the adulthood as well as in newborn infants. However, experimental in vitro and in vivo studies have shown that bevacizumab has also the capacity of causing adverse ocular effects on cellular processes interfering in proliferative and differentiation retinal processes. Based on the current knowledge on pathogenesis of retinal diseases, the current study has the purpose of investigating bevacizumab effect on cellular and molecular mechanisms of the retina, particularly the differentiation mechanisms, growth factors and retinal proteoglycans that support such events. In the study, biochemical and molecular biology techniques will be employed to provide quantitative and gene expression analysis. Immunocytochemistry assays and LUMINEX immunoassays will be employed. mRNA expression will be analyzed using reverse transcriptase reaction, in which amplification of selected sequences will be performed using real-time polymerase chain reaction. Findings in this study will hopefully bring important insights for future studies regarding synthesis of markers and the effect of anti-angiogenic drugs in the retina as well as for the knowledge about mechanisms of action that will be important for designing new treatment options. (AU)

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
MATSUDA, MONIQUE; KREMPEL, PALOMA GAVA; MARQUEZINI, MONICA VALERIA; SHOLL-FRANCO, ALFRED; LAMEU, AMANDA; MONTEIRO, MARIO LUIZ R.; DE OLIVEIRA MIGUEL, NADIA CAMPOS. Cellular stress response in human Milner cells (MIO-M1) after bevacizumab treatment. EXPERIMENTAL EYE RESEARCH, v. 160, p. 1-10, JUL 2017. Web of Science Citations: 2.
KREMPEL, PALOMA G.; MATSUDA, MONIQUE; MARQUEZINI, MONICA V.; SEIXAS, THAYANE G.; VENTURA, GRASIELLA M.; SHOLL-FRANCO, ALFRED; MIGUEL, NADIA C. O.; MONTEIRO, MARIO L. R. Bevacizumab Reduces Neurocan Content and Gene Expression in Newborn Rat Retina In Vitro. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, v. 55, n. 8, p. 5109-5115, AUG 2014. Web of Science Citations: 3.

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