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Updated: Apr 13, 2026
Use of Rabbit Eyes in Pharmacokinetic Studies of Intraocular Drugs
Published on: July 23, 2016
Cytotoxicity and genotoxicity of intravitreal adalimumab administration in rabbit retinal cells
Álcio Coutinho de Paula1, Marcos Pereira de Ávila1, David Leonardo Cruvinal Isaac1
1Ophthalmic Center Reference, Federal University of Goiás, Goiânia, GO, Brazil.
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.
Insights
Intravitreal adalimumab (a TNF-α inhibitor) showed no cytotoxicity or genotoxicity in rabbit retinal cells up to 60 days. This suggests adalimumab is a safe option for treating ocular inflammatory diseases.
Area of Science:
- Ophthalmology
- Toxicology
- Molecular Biology
Background:
- Tumor Necrosis Factor-alpha (TNF-α) plays a key role in ocular inflammatory diseases.
- Adalimumab is a biologic agent targeting TNF-α, with potential for intravitreal administration.
- Assessing the safety profile, specifically cytotoxicity and genotoxicity, is crucial before clinical application.
Purpose of the Study:
- To evaluate the cytotoxicity and genotoxicity of intravitreal adalimumab in a rabbit model.
- To utilize cytological and molecular techniques for comprehensive safety assessment.
Main Methods:
- Rabbits were divided into control, adalimumab, and placebo groups.
- Cytotoxicity assessed via flow cytometry for apoptosis and necrosis.
- Genotoxicity evaluated using comet assays for DNA damage and qPCR for caspase gene expression.
Main Results:
- No significant cytotoxicity or genotoxicity was observed in adalimumab or placebo groups compared to controls.
- Over 90% cell viability was maintained; low levels of apoptosis (~10%) and necrosis (<1%) were noted across all groups.
- Minimal DNA degradation (<6.4%) and no increase in apoptosis-related caspase gene expression were detected.
Conclusions:
- Intravitreal adalimumab demonstrated no detectable cytotoxicity or genotoxicity in retinal cells for up to 60 days.
- These findings support adalimumab as a potentially safe intravitreal treatment for ocular inflammatory conditions involving TNF-α.
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