Safety of intravitreal injection of recombinant human endostatin in rabbits

Authors: Xia Ying,  Chen Fang,  Du Wei,  Zhu Jun,  Jia Shuya,  Ma Haiying,  Xie Zhenggao

DOI: 10.3760/cma.j.cn115989-20201104-00744
Published 2021-01-10
Cite as Chin J Exp Ophthalmol, 2021,39(01): 1-6.

Abstract

Objective

To investigate and evaluate the safety of intravitreal injection of recombinant human endostatin (rh-endostatin) with different concentrations in rabbit eyes.

Methods

Thirty healthy adult New Zealand white rabbits were enrolled with the right eyes selected as experimental eyes, and were randomly divided into five groups by random distribution of computer numbers, with 6 eyes in each group.The rabbits in the normal control group were given no treatment, and the rabbits in the normal saline group, 0.125 mg rh-endostatin group, 0.250 mg rh-endostatin group and 0.500 mg rh-endostatin group were treated with 100 μl of normal saline, 0.125 mg/100 μl, 0.250 mg/100 μl and 0.500 mg/100 μl rh-endostatin according to grouping, respectively.The anterior segment and fundus of the experimental eyes were examined using slit lamp biomicroscope and indirect ophthalmoscope, and the intraocular pressure (IOP) of the experimental eyes were measured with iCARE handheld tonometer before injection and 1 day, 3, 7, 14, 30 and 60 days after injection.Optical coherence tomography (OCT) examination was performed before the intravitreal injection and 7, 30, and 60 days after injection, respectively.Flash electroretinogram was performed before intravitreal injection and 14 days and 60 days after injection.The rabbits were sacrificed by euthanasia at 60th day after injection.Three experimental eyes of each group were dissected and made into paraffin section, and histopathological staining was used to detect the retinal structural changes.The retinal tissue was separated from the other three study eyes in each group, and the transmission electron microscope was employed to observe the ultrastructural changes of the retina.All animal experiments were performed in adherence to the Regulations of the State and the Animal Center of Yangzhou University Medical College for the Use of Animals in Research.

Results

After intravitreal injection, no obvious anterior or posterior chamber change was observed by slit lamp microscopy in all groups at any time point.Flocculent seepage was observed in one eye of the 0.125 mg and 0.500 mg rh-endostatin group, respectively, which was then absorbed completely on the 7th and 14th day.OCT examination showed no abnormal light reflection or morphological changes in fundus of day after injection in all the groups.There was no significant difference in IOP, a-wave and b-wave amplitude among all the groups at different time points (Fgroup=0.134, 0.101, 0.476; Ftime=1.709, 2.479, 1.706; all at P>0.05). Neither light nor electron microscopy showed any retinal damage in any group.

Conclusions

Intravitreal injection of rh-endostatin is safe at the dosage of 0.125-0.500 mg in rabbits.

Key words:

Endostatin; Intravitreal injections; Ocular toxicity; Rabbit

Contributor Information

Xia Ying
Department of Ophthalmology, Affiliated Subei People’s Hospital to Yangzhou University, Yangzhou 225001, China
Chen Fang
Department of Ophthalmology, Affiliated Subei People’s Hospital to Yangzhou University, Yangzhou 225001, China
Du Wei
Department of Ophthalmology, Affiliated Subei People’s Hospital to Yangzhou University, Yangzhou 225001, China
Zhu Jun
Department of Ophthalmology, Affiliated Subei People’s Hospital to Yangzhou University, Yangzhou 225001, China
Jia Shuya
Department of Ophthalmology, Affiliated Subei People’s Hospital to Yangzhou University, Yangzhou 225001, China
Ma Haiying
Department of Ophthalmology, Affiliated Subei People’s Hospital to Yangzhou University, Yangzhou 225001, China
Xie Zhenggao
Xie Zhenggao is now working at the Department of Ophthalmology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China
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Updated: January 26, 2021 — 6:48 am