In Vitro Effects of Bevacizumab Treatment on Newborn Rat Retinal Cell Proliferation, Death, and Differentiation

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art_MIGUEL_In_Vitro_Effects_of_Bevacizumab_Treatment_on_Newborn_2012.PDF (359.79 KB)
Citações na Scopus
16
Tipo de produção
article
Data de publicação
2012
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
ASSOC RESEARCH VISION OPHTHALMOLOGY INC
Autores
ALLODI, Silvana
MENDEZ-OTERO, Rosalia
PUNTAR, Thiago
SHOLL-FRANCO, Alfred
KREMPEL, Paloma G.
Citação
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, v.53, n.12, p.7904-7911, 2012
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
PURPOSE. Vascular endothelial growth factor (VEGF) is an important signal protein in vertebrate nervous development, promoting neurogenesis, neuronal patterning, and glial cell growth. Bevacizumab, an anti-VEGF agent, has been extensively used for controlling pathological retinal neovascularization 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 cell death, proliferation, and differentiation 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 2 days. Immunohistochemical staining was assessed against proliferating cell nuclear antigen (PCNA, to detect cell proliferation); caspase-3 and beclin-1 (to investigate cell death); and vimentin and glial fibrillary acidic protein (GFAP, markers of glial cells). Gene expressions were quantified by real-time reverse-transcription polymerase chain reaction. Results from treatment and control groups were compared. RESULTS. No significant difference in the staining intensity (on immunohistochemistry) of PCNA, caspase-3, beclin-1, and GFAP, or in the levels of PCNA, caspase-3, beclin-1, and vimentin mRNA was observed between the groups. However, a significant increase in vimentin levels and a significant decrease in GFAP mRNA expression were observed in bevacizumab-treated retinal explants compared with controls. CONCLUSIONS. Bevacizumab did not affect cell death or proliferation in early developing rat retina but appeared to interfere with glial cell maturation by increasing vimentin levels and downregulating GFAP gene expression. Thus, we suggest anti-VEGF agents be used with caution in developing retinal tissue.
Palavras-chave
URI
https://observatorio.fm.usp.br/handle/OPI/912
Referências
  1. Akkoyun I, 2012, ACTA OPHTHALMOL, V90, P564, DOI 10.1111/j.1755-3768.2010.01963.x
  2. Alexiades MR, 1996, DEV DYNAM, V205, P293, DOI 10.1002/(SICI)1097-0177(199603)205:3<293::AID-AJA9>3.0.CO;2-D
  3. Avery RL, 2006, OPHTHALMOLOGY, V113, P1695, DOI 10.1016/j.ophtha.2006.05.064
  4. Bakri SJ, 2006, AM J OPHTHALMOL, V142, P162, DOI 10.1016/j.ajo.2006.03.058
  5. Baye LM, 2007, J NEUROSCI, V27, P10143, DOI 10.1523/JNEUROSCI.2754-07.2007
  6. Bock F, 2007, INVEST OPHTH VIS SCI, V48, P2545, DOI 10.1167/iovs.06-0570
  7. Bock F, 2008, GRAEF ARCH CLIN EXP, V246, P281, DOI 10.1007/s00417-007-0684-4
  8. Brar VS, 2010, MOL VIS, V16, P1848
  9. Bringmann A, 2009, NEUROCHEM INT, V54, P143, DOI 10.1016/j.neuint.2008.10.014
  10. Darland DC, 2003, DEV BIOL, V264, P275, DOI 10.1016/S0012-1606(03)00492-5
  11. da Silva AGLS, 2008, J NEUROIMMUNOL, V196, P82, DOI 10.1016/j.jneuroim.2008.03.003
  12. DEGUEVARA R, 1994, CR ACAD SCI III-VIE, V317, P737
  13. DRAGER UC, 1983, NATURE, V303, P169, DOI 10.1038/303169a0
  14. DVORAK HF, 1995, INT ARCH ALLERGY IMM, V107, P233
  15. Feiner L, 2006, RETINA-J RET VIT DIS, V26, P882, DOI 10.1097/01.iae.0000230717.85319.f5
  16. Ferrara Napoleone, 2000, Current Opinion in Biotechnology, V11, P617, DOI 10.1016/S0958-1669(00)00153-1
  17. Ferrara N, 2003, NAT MED, V9, P669, DOI 10.1038/nm0603-669
  18. Ferrara N, 1997, ENDOCR REV, V18, P4, DOI 10.1210/er.18.1.4
  19. Fulton AB, 2009, DOC OPHTHALMOL, V118, P55, DOI 10.1007/s10633-008-9127-8
  20. Fusco MA, 2012, CLINICS, V67, P1
  21. Guimaraes CA, 2003, J BIOL CHEM, V278, P41938, DOI 10.1074/jbc.M306547200
  22. Gunther JB, 2009, SURV OPHTHALMOL, V54, P372, DOI 10.1016/j.survophthal.2009.02.004
  23. Guo B, 2010, MOL VIS, V16, P793
  24. Hashemian MN, 2011, OPHTHALMIC RES, V46, P50, DOI 10.1159/000322061
  25. Iandiev I, 2011, GRAEF ARCH CLIN EXP, V249, P1821, DOI 10.1007/s00417-011-1773-y
  26. Inan UU, 2007, INVEST OPHTH VIS SCI, V48, P1773, DOI 10.1167/iovs.06-0828
  27. Kim K J, 1992, Growth Factors, V7, P53, DOI 10.3109/08977199209023937
  28. Linden R, 1999, PROG RETIN EYE RES, V18, P133, DOI 10.1016/S1350-9462(98)00020-2
  29. Luthra S, 2006, RETINA-J RET VIT DIS, V26, P512, DOI 10.1097/01.iae.0000222547.35820.52
  30. Ma J, 2010, CLIN EXP OPHTHALMOL, V38, P875, DOI 10.1111/j.1442-9071.2010.02370.x
  31. Manzano RPA, 2007, BRIT J OPHTHALMOL, V91, P804, DOI 10.1136/bjo.2006.107912
  32. Manzano RPA, 2006, RETINA-J RET VIT DIS, V26, P257, DOI 10.1097/00006982-200603000-00001
  33. Mintz-Hittner HA, 2011, NEW ENGL J MED, V364, P603, DOI 10.1056/NEJMoa1007374
  34. Moshfeghi DM, 2011, OPHTHALMOLOGY, V118, P1227, DOI 10.1016/j.ophtha.2011.04.028
  35. Nishijima K, 2007, AM J PATHOL, V171, P53, DOI 10.2353/ajpath.2007.061237
  36. PERRY VH, 1983, J COMP NEUROL, V219, P356, DOI 10.1002/cne.902190309
  37. Peters S, 2007, AM J OPHTHALMOL, V143, P995, DOI 10.1016/j.ajo.2007.03.007
  38. Rosenstein JM, 2010, ORGANOGENESIS, V6, P107, DOI 10.4161/org.6.2.11687
  39. Rosenstein JM, 2004, EXP NEUROL, V187, P246, DOI 10.1016/j.expneurol.2004.01.022
  40. Rubaltelli David Maria, 2008, Int Ophthalmol Clin, V48, P225, DOI 10.1097/IIO.0b013e318169544f
  41. Saint-Geniez M, 2006, INVEST OPHTH VIS SCI, V47, P3135, DOI 10.1167/iovs.05-1229
  42. Saint-Geniez M, 2008, PLOS ONE, V3, P3554
  43. Shahar J, 2006, RETINA-J RET VIT DIS, V26, P262, DOI 10.1097/00006982-200603000-00002
  44. SHAW G, 1983, EUR J CELL BIOL, V30, P219
  45. Spaide RF, 2006, RETINA-J RET VIT DIS, V26, P275, DOI 10.1097/00006982-200603000-00004
  46. Spandau U, 2013, ACTA OPHTHALMOL, V91, P170, DOI 10.1111/j.1755-3768.2011.02351.x
  47. Stewart MW, 2012, MAYO CLIN PROC, V87, P77, DOI 10.1016/j.mayocp.2011.10.001
  48. Thaler S, 2010, ACTA OPHTHALMOL, V88, pE170, DOI 10.1111/j.1755-3768.2010.01927.x
  49. Waisbourd M, 2010, ACTA OPHTHALMOL, V89, P203
  50. Walcott JC, 2003, CLIN EXP OPHTHALMOL, V31, P246, DOI 10.1046/j.1442-9071.2003.00638.x
  51. Wu WC, 2011, OPHTHALMOLOGY, V118, P176, DOI 10.1016/j.ophtha.2010.04.018
  52. Yu LL, 2008, INVEST OPHTH VIS SCI, V49, P522, DOI 10.1167/iovs.07-1175
  53. Zachary I, 2005, NEUROSIGNALS, V14, P207, DOI 10.1159/000088637
  54. Zayit-Soudry S, 2011, RETINA-J RET VIT DIS, V31, P1885, DOI 10.1097/IAE.0b013e31821a88e2

Coleções
Artigos e Materiais de Revistas Científicas - FM/MOF
Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - LIM/33