Cytotoxicity and genotoxicity of intravitreal adalimumab administration in rabbit retinal cells
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Data
2015
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Resumo
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. Ge-
notoxicity 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 addi-
tion, 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.
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Palavras-chave
Intravitreal injections, Animals, Rabbits, Retina, Antibodies, monoclonal, humanized/ toxicity, Tumor necrosis factor alpha, Apoptosis, Retina, Injecções intravítreas, Coelhos, Anticorpos monoclonais humanizados/ toxicidade, Animais, Fator de necrose tumoral alfa, Apoptose
Citação
PAULA, Álcio Coutinho de; ÁVILA, Marcos Pereira de; ISAAC, David Leonardo Cruvinal; SALUSTIANO, Rodrigo; LIMA, Aliny Pereira de; MELLO, Francyelli Mariana; PEREIRA, Flávia de Castro; SILVA, Pedro Henrique de Paula; LACERDA, Elisângela de Paula Silveira. Cytotoxicity and genotoxicity of intravitreal adalimumab administration in rabbit retinal cells. Arquivos Brasileiros de Oftalmologia, São Paulo, v. 78, n. 2, p. 89-93, 2015.