Hines J, Vinores S A, Campochiaro P A
Wilmer Ophthalmological Institute, Johns Hopkins Hospital, Baltimore, MD 21287.
Curr Eye Res. 1993 Jun;12(6):521-9. doi: 10.3109/02713689309001830.
Gentamicin shows retinal toxicity in rabbits, monkeys, and humans, but its mechanism of toxicity is not understood. Pig eyes, which are anatomically similar to human eyes, were examined with ophthalmoscopy, fluorescein angiography, and light and electron microscopy at time points ranging from 3 to 72 hours after intravitreous injection of 3 mg of gentamicin or vehicle to observe the sequence of toxicity-related changes that occur in the retina. The first ophthalmoscopic changes were retinal hemorrhages at 3 hours, followed by retinal whitening and thickening and vascular nonperfusion detected by fluorescein angiography 48 hours after injection. Vacuolization in the nerve fiber layer and perivascular swelling were seen at 6 hours, and subsequently, extended deeper into the retina. Vascular endothelial cells, photoreceptors, and the retinal pigment epithelium appeared to be spared from the toxic effects of gentamicin. At 48 and 72 hours after injection, numerous large and small retinal vessels showed congestion and leukocyte margination. These changes could not be prevented by increasing the pH of gentamicin to 7.2. These data suggest that gentamicin toxicity is not simply a pH-related phenomenon, that the primary targets of gentamicin toxicity are neurons and glia of the inner retina, and that retinal infarction occurs secondarily, possibly due to leukocytic plugging.
庆大霉素对兔、猴和人类均显示出视网膜毒性，但其毒性机制尚不清楚。猪眼在解剖结构上与人类眼睛相似，在玻璃体内注射3毫克庆大霉素或赋形剂后的3至72小时内，通过检眼镜检查、荧光素血管造影以及光镜和电镜观察视网膜中与毒性相关变化的发生顺序。最初的检眼镜检查变化是在3小时出现视网膜出血，随后在注射后48小时通过荧光素血管造影检测到视网膜变白、增厚以及血管无灌注。在6小时可见神经纤维层空泡化和血管周围肿胀，随后病变向视网膜深部扩展。血管内皮细胞、光感受器和视网膜色素上皮似乎未受庆大霉素毒性影响。在注射后48小时和72小时，许多大小不等的视网膜血管出现充血和白细胞靠边现象。将庆大霉素的pH值提高到7.2并不能预防这些变化。这些数据表明，庆大霉素毒性并非仅仅是与pH相关的现象，庆大霉素毒性的主要靶点是视网膜内层的神经元和神经胶质细胞，视网膜梗死可能继发于白细胞阻塞。
