Systemic effects after intravitreal injection of bevacizumab in new born rabbit eyes

Abstract

Purpose: To determine the systemic impact of intravitreal injection of bevacizumab (IVB), an anti-vascular endothelium growth factor antibody, in newborn rabbits.

Materials and methods: We used four groups of rabbits. Group 1 rabbits received a single injection of IVB starting from the age of 6 weeks. Group 2 rabbits received a single injection of balanced salt solution (BSS, 0.025 ml) and served as controls for group 1. Group 3 rabbits received two consecutive injections of IVB at the ages of 6 and 10 weeks. Group 4 rabbits received two consecutive injections of BSS at the ages of 6 and 10 weeks and served as controls for group 3. During the experiment, a complete blood count (CBC), clinical biochemistry, weight gain, food intake, body temperature, blood pressure, pulse, and mortality were measured in the animals. Two months after IVB injection, the animals were sacrificed, and histology of the major organs was checked. Immunohistochemistry was assessed to explore the neurons in the central nervous system (CNS).

Results: We found there were no morphological or functional changes in the eyes following IVB injection. Furthermore, there were no differences in CBC, biochemistry, or other measured parameters among the four groups of animals. We checked the histology of the major organs and neurons in the CNS and they did not reveal significant differences among the four groups of animals.

Conclusions: Conclusively, IVB of either one or two injections (0.625 mg) in newborn rabbit eyes is well tolerated and does not cause noticeable systemic organ pathology.

Keywords:

• Bevacizumab
• intravitreal injection
• retinopathy of prematurity
• vascular endothelial growth factor

Acknowledgements

This study was supported by the Chang Gung Memorial Hospital, Taoyuan, Taiwan [grant Nos. CMRPG3E05212 and CMRPG3F01913]; and the Ministry of Science and Technology of the Republic of China [grant No. MOST104–2314-B-182A-100-MY2]. The study was helped by the Microscope Core Laboratory, Chang Gung Memorial Hospital, Linkou and the Laboratory Animal Center, Chang Gung Memorial Hospital, Linkou.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Additional information

Funding

This study was supported by the Chang Gung Memorial Hospital, Taoyuan, Taiwan [grant Nos. CMRPG3E05212 and CMRPG3F01913]; and the Ministry of Science and Technology of the Republic of China [grant No. MOST104–2314-B-182A-100-MY2].