Cytotoxicity and genotoxicity of intravitreal adalimumab administration in rabbit retinal cells

Arquivos Brasileiros de Oftalmologia

Álcio Coutinho De Paula¹  Marcos Pereira De Ávila¹  David Leonardo Cruvinal Isaac¹  Rodrigo Salustiano¹  Aliny Pereira De Lima¹  Francyelli Mariana Mello¹  Flávia De Castro Pereira¹  Pedro Henrique De Paula Silva¹  Elisângela De Paula Silveira Lacerda¹ 

关键词: Intravitreal injections;    Retina;    Antibodies;    monoclonal;    humanized/toxicity;    Apoptosis;    Tumor necrosis factor alpha;    Animals;    RabbitsInjecções intravítreas;    ;    Retina;    Anticorpos monoclonais humanizados/toxicidade;    Apoptose;    Fator de necrose tumoral alfa;    Animais;    Coelhos;   

DOI  :  10.5935/0004-2749.20150024

来源: SciELO

【 摘 要 】

Purpose: To assess the cytotoxicity and genotoxicity of intravitreal adalimumab treatment in an animal experimental model using cytological and molecular techniques. Methods: Eighteen rabbits were randomly assigned to three groups: control, adalimumab treatment, and placebo. Cytotoxicity on retinal cells was evaluated using flow cytometry assays to determine the level of apoptosis and necrosis. Genotoxicity was evaluated by comet assays to assess DNA damage, and quantitative real-time polymerase chain reaction (qPCR) was used to evaluate expression of apoptosis-inducing caspases (8 and 3). Results: No cytotoxicity or genotoxicity was observed in any of the two treatment groups (adalimumab and placebo) following intravitreal administration compared with the control group. Flow cytometry analysis revealed that more than 90% of the cells were viable, and only a low proportion of retinal cells presented apoptotic (~10%) or necrotic (<1%) activity across all groups. Molecular damage was also low with a maximum of 6.4% DNA degradation observed in the comet assays. In addition, no increase in gene expression of apoptosis-inducing caspases was observed on retinal cells by qPCR in both the adalimumab and placebo groups compared with the control group. Conclusion: The use of adalimumab resulted in no detectable cytotoxicity or genotoxicity on retinal cells for up to 60 days upon administration. These results therefore indicate that adalimumab may be a safe option for intravitreal application to treat ocular inflammatory diseases in which TNF-α is involved.

【 授权许可】

CC BY   
 All the contents of this journal, except where otherwise noted, is licensed under a Creative Commons Attribution License