Preclinical Investigations of Intravitreal Ziv-Aflibercept

被引:33
作者
de Oliveira Dias, Joao Rafael [1 ]
Badaro, Emmerson [1 ]
Novais, Eduardo Amorim [1 ]
Colicchio, Daniel [1 ]
Denadai Chiarantin, Gabrielly Maria [2 ]
Matioli, Mariana Mauricio [1 ]
Verna, Carina [1 ]
Penha, Fernando Marcondes [1 ]
Tenorio Barros, Nilana Meza [2 ]
Meyer, Carsten H. [1 ]
Farah, Michel Eid [1 ]
Rodrigues, Eduardo Buchele [1 ]
机构
[1] Univ Fed Sao Paulo, Dept Ophthalmol, Sao Paulo, Brazil
[2] Univ Fed Sao Paulo, Dept Biophys, Sao Paulo, Brazil
关键词
METASTATIC COLORECTAL-CANCER; VEGF TRAP-EYE; MACULAR DEGENERATION; RETINAL-DETACHMENT; IN-VITRO; BEVACIZUMAB; RANIBIZUMAB; INJECTION; DRUGS; NEOVASCULARIZATION;
D O I
10.3928/23258160-20141118-15
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
BACKGROUND AND OBJECTIVE: To investigate the retinal safety of intravitreal (IVT) ziv-aflibercept in rabbits. MATERIALS AND METHODS: Eighteen rabbits were given an IVT injection of ziv-aflibercept (25 mg/mL) or aflibercept (40 mg/mL) and examined by funduscopy, electroretinography (ERG), optical coherence tomography (OCT), light microscopy, and transmission electron microscopy (TEM). Serum, aqueous, and vitreous were obtained afterward for osmolarity analysis. The effect of ziv-aflibercept on human retinal cultured cells (ARPE-19) was assessed by the MTT cell viability assay. RESULTS: All eyes showed normal funduscopy, OCT, and ERG findings at baseline and 24 hours or 7 days after the procedure. Median baseline serum, vitreous, and aqueous osmolarity remained unchanged. Histology and TEM showed no major anatomic signs of toxicity. No cytotoxic effect was observed in ARPE-19 cells exposed to ziv-aflibercept. CONCLUSION: IVT injection ziv-aflibercept at a concentration of 25 mg/mL proved to be safe for the rabbit retina.
引用
收藏
页码:577 / 584
页数:8
相关论文
共 26 条
[11]   Intravitreal Aflibercept (VEGF Trap-Eye) in Wet Age-related Macular Degeneration [J].
Heier, Jeffrey S. ;
Brown, David M. ;
Chong, Victor ;
Korobelnik, Jean-Francois ;
Kaiser, Peter K. ;
Quan Dong Nguyen ;
Kirchhof, Bernd ;
Ho, Allen ;
Ogura, Yuichiro ;
Yancopoulos, George D. ;
Stahl, Neil ;
Vitti, Robert ;
Berliner, Alyson J. ;
Soo, Yuhwen ;
Anderesi, Majid ;
Groetzbach, Georg ;
Sommerauer, Bernd ;
Sandbrink, Rupert ;
Simader, Christian ;
Schmidt-Erfurth, Ursula .
OPHTHALMOLOGY, 2012, 119 (12) :2537-2548
[12]   The 1-year Results of CLEAR-IT 2, a Phase 2 Study of Vascular Endothelial Growth Factor Trap-Eye Dosed As-needed After 12-week Fixed Dosing [J].
Heier, Jeffrey S. ;
Boyer, David ;
Quan Dong Nguyen ;
Marcus, Dennis ;
Roth, Daniel B. ;
Yancopoulos, George ;
Stahl, Neil ;
Ingerman, Avner ;
Vitti, Robert ;
Berliner, Alyson J. ;
Yang, Ke ;
Brown, David M. .
OPHTHALMOLOGY, 2011, 118 (06) :1098-1106
[13]   VEGF-Trap: A VEGF blocker with potent antitumor effects [J].
Holash, J ;
Davis, S ;
Papadopoulos, N ;
Croll, SD ;
Ho, L ;
Russell, M ;
Boland, P ;
Leidich, R ;
Hylton, D ;
Burova, E ;
Ioffe, E ;
Huang, T ;
Radziejewski, C ;
Bailey, K ;
Fandl, JP ;
Daly, T ;
Wiegand, SJ ;
Yancopoulos, GD ;
Rudge, JS .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (17) :11393-11398
[14]   Mean overall survival gain with aflibercept plus FOLFIRI vs placebo plus FOLFIRI in patients with previously treated metastatic colorectal cancer [J].
Joulain, F. ;
Proskorovsky, I. ;
Allegra, C. ;
Tabernero, J. ;
Hoyle, M. ;
Iqbal, S. U. ;
Van Cutsem, E. .
BRITISH JOURNAL OF CANCER, 2013, 109 (07) :1735-1743
[15]   Effect of bevacizumab (Avastin TM ) on mitochondrial function of in vitro retinal pigment epithelial, neurosensory retinal and microvascular endothelial cells [J].
Luthra, Saurabh ;
Sharma, Ashish ;
Dong, Joyce ;
Neekhra, Aneesh ;
Gramajo, Ana L. ;
Seigel, Gail M. ;
Kenney, M. Cristina ;
Kuppermann, Baruch D. .
INDIAN JOURNAL OF OPHTHALMOLOGY, 2013, 61 (12) :705-710
[16]  
MARMOR MF, 1979, INVEST OPHTH VIS SCI, V18, P1237
[17]  
MARMOR MF, 1980, INVEST OPHTH VIS SCI, V19, P1016
[18]   Ranibizumab and Bevacizumab for Neovascular Age-Related Macular Degeneration The CATT Research Group [J].
Martin, Daniel F. ;
Maguire, Maureen G. ;
Ying, Gui-shuang ;
Grunwald, Juan E. ;
Fine, Stuart L. ;
Jaffe, Glenn J. .
NEW ENGLAND JOURNAL OF MEDICINE, 2011, 364 (20) :1897-1908
[19]   TOXICITY AND RETINAL PENETRATION OF INFLIXIMAB IN PRIMATES [J].
Melo, Gustavo B. ;
Moraes Filho, Milton N. ;
Rodrigues, Eduardo B. ;
Regatieri, Caio V. ;
Dreyfuss, Juliana L. ;
Penha, Fernando M. ;
Pinheiro, Marcelo M. ;
Coimbra, Rita C. S. G. ;
Haapalainen, Edna F. ;
Farah, Michel E. .
RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES, 2012, 32 (03) :606-612
[20]   Preclinical aspects of anti-VEGF agents for the treatment of wet AMD: ranibizumab and bevacizumab [J].
Meyer, C. H. ;
Holz, F. G. .
EYE, 2011, 25 (06) :661-672