Cam Duygu, Saatci Ali Osman, Micili Serap Cilaker, Ergur Bekir Ugur, Karabag Revan Yildirim, Durak Ismet, Berk Ayse Tulin
Department of Ophthalmology, State Hospital, Tunceli, Turkey.
Department of Ophthalmology, Dokuz Eylul University, Izmir, Turkey.
Open Ophthalmol J. 2016 Feb 4;10:12-6. doi: 10.2174/1874364101610010012. eCollection 2016.
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.
在新生兔模型中评估玻璃体内注射阿奇霉素对视网膜的影响。
将12只两周大的新西兰白化兔分为两组（每组6只）。6只兔子的右眼玻璃体内注射0.75mg（0.05mL）阿奇霉素，其余6只兔子的右眼玻璃体内注射1.5mg（0.1mL）阿奇霉素。左眼作为对照，注射相同体积的生理盐水。在注射后第三周摘除所有眼球。通过光学显微镜检查视网膜组织学。通过免疫组织化学染色检测caspase-3以及对DNA片段进行原位末端脱氧核苷酸转移酶介导的生物素-脱氧尿苷三磷酸缺口末端标记（TUNEL），进一步评估视网膜细胞的凋亡情况。
光学显微镜检查显示所有眼球的视网膜均无异常。然而，采用TUNEL法时，两个研究组均出现明显的视网膜核DNA片段化（1.5mg阿奇霉素组为33.6%，0.75mg阿奇霉素组为21.4%）。与对照组相比，仅1.5mg阿奇霉素治疗的第二组TUNEL染色率具有统计学意义上的升高（曼-惠特尼U检验，p = 0.01）。两个研究组中caspase-3阳性细胞的比例分别为21.5%和20.2%。与对照眼相比，两个研究组的caspase-3染色率均具有统计学意义上的升高（分别为p = 0.00，p = 0.00）。两个研究组之间TUNEL染色率的差异具有统计学意义（p = 0.028），但通过caspase-3染色，两个研究组之间无统计学意义上的差异（p = 0.247）。
在新生兔中，玻璃体内注射阿奇霉素可导致光感受器、双极细胞和神经节细胞出现凋亡活性。免疫组织化学分析表明，玻璃体内注射0.75mg和1.5mg阿奇霉素剂量可能对新生兔视网膜有毒性。
