Abstract
Purpose:
To evaluate the effect of intravitreal azithromycin on the retina in a newborn rabbit model.
Methods:
Twelve, two-week old New Zealand albino rabbits were used for this study and divided into two groups (six in each). The first group received 0.75 mg (0.05 mL) intravitreal azithromycin, and the second group received 1.5 mg (0.1 mL) intravitreal azithromycin. The right eyes were designated as the study eyes, and the left eyes were served as the control and received the same volume of saline intravitreally. Eyes were enucleated at the third postinjection week. Histopathology and retinal morphology were examined by light microscopy. Apoptosis in the retinal cells was evaluated by immunohistochemical staining for caspase-3 and in situ terminal deoxynucleotidyl transferase-mediated biotin-deoxyuridine triphosphate nick-end labeling (TUNEL) of DNA fragments.
Results:
Light microscopy showed no detectable pathological changes in the retina. However, nuclear DNA fragmentation was evident in the retinal layers in the two dose groups (33.6% with 0.1mL and 21.4% with 0.05 mL azithromycin) with the TUNEL method. TUNEL staining ratio was found to be statistically higher only in the second group injected with 1.5 mg azithromycin when compared to the control group (p=0.01 Mann Whitney U test). The ratios of caspase-3 positive cells in two groups were 21.5% and 20.2%, respectively. Caspase-3 staining ratio were found to be statistically higher in the eyes injected with either 0.75 mg or 1.5 mg azithromycin when compared to the control eyes (p=0.00, p=0.00 respectively). The difference of TUNEL staining ratio between the two groups was statistically significant (p=0.028), but there were no statistically significant differences in the two groups by caspase-3 staining (p=0.247).
Conclusions:
In newborn rabbits, intravitreal azithromycin injection caused an apoptotic activity in the photoreceptor, bipolar and ganglion cells. Histologic findings indicated that a dose of 0.75 mg and 1.5 mg azithromycin, administered intravitreally might be toxic to the rabbit retina.