Bevacizumab Reduces Neurocan Content and Gene Expression in Newborn Rat Retina In Vitro

Autor(es)

Krempel, Paloma G. ^[1] ; Matsuda, Monique ^[1] ; Marquezini, Monica V. ^{[2, 3]} ; Seixas, Thayane G. ^[4] ; Ventura, Grasiella M. ^[5] ; Sholl-Franco, Alfred ^[6] ; Miguel, Nadia C. O. ^[5] ; Monteiro, Mario L. R. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Med, Lab Invest Ophthalmol LIM 33, Sao Paulo - Brazil

^[2] ProSangue Fdn, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Sch Med, Dept Pathol, Expt Air Pollut Lab, Sao Paulo - Brazil

^[4] Univ Fed Rio de Janeiro, Coll Pharm, Rio de Janeiro - Brazil

^[5] Univ Fed Rio de Janeiro, Inst Biomed Sci, Program Cell & Dev Biol, Rio de Janeiro - Brazil

^[6] Univ Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, Neurogenese Lab, Program Neurobiol, BR-21941 Rio De Janeiro - Brazil

• Tipo de documento: Artigo Científico
• Fonte: INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE; v. 55, n. 8, p. 5109-5115, AUG 2014.
• Citações Web of Science: 3

Resumo

PURPOSE. Extracellular matrix (ECM) and cellular membrane proteoglycans (PGs) play important roles in neural differentiation and cell adhesion. Vascular endothelial growth factor, an important signal protein in vascular and retinal neural cell development, is retained in the ECM due to its high affinity for PG. Bevacizumab, an anti-VEGF agent, has been extensively used for treating retinal diseases in adult and newborn patients, although its effect on the developing retina remains largely unknown. The purpose of this study was to investigate the effect of bevacizumab on neurocan, phosphacan, and syndecan-3 PG levels in newborn rat retina. METHODS. Retinal explants of sixty 2-day-old Lister hooded rats were obtained after eye enucleation and maintained in culture media with or without bevacizumab for 48 hours. Immunohistochemical staining was assessed against neurocan, phosphacan, and syndecan-3. Proteoglycan content was quantified based on the intensity of immunohistochemical labeling. Gene expressions were quantified by real-time reverse-transcription polymerase chain reaction. The results from the treatment and control groups were compared. RESULTS. No significant difference in the staining intensity and mRNA expression of phosphacan and syndecan-3 was observed between the groups. However, a significant decrease in neurocan content and mRNA expression was observed in bevacizumab-treated retinal explants compared with controls. CONCLUSIONS. Bevacizumab did not affect phosphacan and syndecan-3 levels but decreased neurocan content and gene expression. Therefore, it may interfere with early postnatal retinal cell differentiation. Although further studies are necessary to confirm our findings, we suggest anti-VEGF agents be used with caution in developing retinal tissue. (AU)

• Processo FAPESP: 11/12271-3 - Análise imunohistoquímica e de expressão gênica dos efeitos do bevacizumabe em explantes de retina de ratos lister e em uma linhagem celular de glia de Müller humana
• Beneficiário: Mário Luiz Ribeiro Monteiro
• Modalidade de apoio: Auxílio à Pesquisa - Regular