The Effect of Intravitreal Azithromycin on the Albino Newborn Rabbit Retina

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 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. Results: 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). Conclusion: 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.

Recent Advances of Ocular Drug Delivery Systems: Prominence of Ocular Implants for Chronic Eye Diseases

“…The current treatment for endophthalmitis involves repeated intravitreal injections of antimicrobial, antifungal, or antiviral agents. This procedure increases the complications and commonly results in blindness by causing irritation, ocular pain, a rise in the intraocular pressure, intraocular hemorrhage, a greater risk of retinal detachment, and retinal damage [ 91 , 92 , 93 , 94 , 95 ]. Consequently, the development of drug delivery systems for antimicrobial, antifungal, or antiviral agents could enhance ocular tissue penetration and activity noninvasively ( Table 1 ).…”