The Effect of Intravitreal Azithromycin on the Albino Newborn Rabbit Retina

Duygu Cam1, Ali Osman Saatci2, *, Serap Cilaker Micili3, Bekir Ugur Ergur3, Revan Yildirim Karabag4, Ismet Durak2, Ayse Tulin Berk2
1 Department of Ophthalmology, State Hospital, Tunceli, Turkey
2 Department of Ophthalmology, Dokuz Eylul University, Izmir, Turkey
3 Department of Histology and Embryology, Dokuz Eylul University, Izmir, Turkey
4 Department of Ophthalmology, State Hospital, Manisa, Turkey

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© Cam et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution-Non-Commercial 4.0 International Public License (CC BY-NC 4.0) (, which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the Department of Ophthalmology, Dokuz Eylul University, Izmir, Turkey; E-mail:



To evaluate the effect of intravitreal azithromycin on the retina in a newborn rabbit model.


Twelve, two-week old New Zealand albino rabbits were divided into two groups (six in each). The right eyes of six rabbits received 0.75 mg (0.05 mL) azithromycin and the right eyes of the remaining six rabbits 1.5 mg (0.1 mL) azithromycin intravitreally. Left eyes were served as the control and received the same volume of saline. All eyes were enucleated at the third postinjection week. Retinal histology was examined by light microscopy. Apoptosis of the retinal cells was further evaluated by immunohistochemical staining for caspase-3 and in situ terminal deoxynucleotidyl transferase-mediated biotin-deoxyuridine triphosphate nick-end labeling (TUNEL) of DNA fragments.


Light microscopy demonstrated no retinal abnormalities in all eyes. However, retinal nuclear DNA fragmentation was evident in both study groups (33.6% with 1.5 mg and 21.4% with 0.75 mg azithromycin) with the TUNEL method. TUNEL staining ratio was statistically higher only in the second group treated with 1.5 mg azithromycin when compared to the control group (p=0.01 Mann Whitney U test). The ratio of caspase-3 positive cells in the two study groups was 21.5% and 20.2%, respectively. Caspase-3 staining ratio was statistically higher in both study groups when compared to the control eyes (p=0.00, p=0.00 respectively). The difference of TUNEL staining ratio between the two study groups was statistically significant (p=0.028), but there were no statistically significant differences in the two study groups by caspase-3 staining (p=0.247).


In newborn rabbits, intravitreal azithromycin injection resulted in an apoptotic activity in the photoreceptor, bipolar and ganglion cells. Immunohistochemical analysis suggested that doses of 0.75 mg and 1.5 mg azithromycin, administered intravitreally might be toxic to the newborn rabbit retina.

Keywords: Azithromycin, apoptic cell death, bacteriostatic agent, retina.