Intravitreal colchicine causes decreased RNFL birefringence without altering RNFL thickness
Intravitreal colchicine causes decreased RNFL birefringence without altering RNFL thickness
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DOI：
10.1167/iovs.07-0872
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发表时间：
2008-01-01
影响因子：
4.4
通讯作者：
Cioffi, George A.
中科院分区：
文献类型：
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作者：
Fortune, Brad;Wang, Lin;Cioffi, George A.
目的。检验以下假设：通过扫描激光偏振仪 (SLP) 测量的视网膜神经纤维层 (RNFL) 双折射和通过光学相干断层扫描 (OCT) 测量的 RNFL 厚度之间的纵向差异可以提供有关轴突变性状态的信息。方法。将秋水仙碱注射到六只黑长尾猴（Chlorocebus sabaeus；估计玻璃体浓度：1 mM，n = 3；2 mM，n = 1；10 mM，n = 2）的一只眼睛的玻璃体腔中；将等量（约 0.1 mL）的无菌盐水注入另一对照眼中。 RNFL双折射在注射前和注射后每10分钟通过SLP测量一次，持续2小时。在注射前和2小时后通过OCT测量RNFL厚度。分离每个视网膜后，使用 2 毫米环钻从距视盘中心约 2 毫米的颞下拱廊区域获取活检标本，并进行透射电子显微镜 (TEM) 处理。然后将视网膜平放并用抗聚合 β-III-微管蛋白的抗体染色。 结果。在所有六只注射秋水仙碱的眼睛中，通过 SLP 测量的 RNFL 双折射随着时间的推移而下降，似乎在注射后约 100 分钟达到 -20% +/- 7% (P < 0.0001) 的平台。象限之间没有显着差异（P = 0.44），并且没有明显的剂量效应（P = 0.87）。注射媒介物的对照眼的变化为-3% +/- 3% (P = 0.06; NS)。通过 OCT 测量的 RNFL 厚度变化在注射秋水仙碱的眼睛中为 +1% +/- 4% (P = 0.81; NS)，在对照眼睛中为 +6% +/- 6% (P = 0.13; NS)。眼底生物显微镜、立体眼底摄影或 OCT 没有发现黄斑水肿的证据。 TEM 显示注射秋水仙碱的眼睛中微管紊乱、线粒体肿胀和轴突膜边界模糊。与对照组相比，用抗聚合β-III-微管蛋白抗体染色的平装视网膜显示，注射秋水仙碱的眼睛中视乳头周围染色强度仅轻度降低。结论。玻璃体内注射秋水仙碱会导致非人灵长类动物眼睛 RNFL 轴突内的微管破坏。这表现为 RNFL 双折射的减少，但 RNFL 厚度没有改变，表明这种差异可以提供有关轴突变性状态的信息。
PURPOSE. To test the hypothesis that longitudinal differences between retinal nerve fiber layer (RNFL) birefringence, measured by scanning laser polarimetry (SLP), and RNFL thickness, measured by optical coherence tomography (OCT), are informative about the state of axonal degeneration.METHODS. Colchicine was injected into the vitreous cavity of one eye in each of six vervet monkeys (Chlorocebus sabaeus; estimated vitreal concentration: 1 mM, n = 3; 2 mM, n = 1; 10 mM, n = 2); an equivalent volume (approximately 0.1 mL) of sterile saline was injected into fellow control eyes. RNFL birefringence was measured by SLP before injection and every 10 minutes after injection for 2 hours. RNFL thickness was measured by OCT before injection and 2 hours later. After isolating each retina, biopsy specimens were obtained from the infero-temporal arcade region, approximately 2 mm from the center of the optic disc, using a 2-mm trephine and were processed for transmission electron microscopy (TEM). Retinas were then flat-mounted and stained with an antibody against polymerized beta-III-tubulin.RESULTS. RNFL birefringence measured by SLP decreased over time in all six colchicine-injected eyes, appearing to reach a plateau of -20% +/- 7% (P < 0.0001) approximately 100 minutes after injection. There were no significant differences between quadrants (P = 0.44) and no apparent dose effect (P = 0.87). The change in vehicle-injected control eyes was -3% +/- 3% (P = 0.06; NS). The change in RNFL thickness measured by OCT was +1% +/- 4% (P = 0.81; NS) in colchicine-injected eyes and +6% +/- 6% (P = 0.13; NS) in control eyes. There was no evidence of macular edema by fundus biomicroscopy, stereo fundus photography, or OCT. TEM revealed disorganization of microtubules, swelling of mitochondria, and blurred axonal membrane borders in colchicine-injected eyes. Flat-mounted retinas stained with an antibody against polymerized beta-III-tubulin showed only a mild reduction of peripapillary stain intensity in the colchicine-injected eyes compared with controls.CONCLUSIONS. Intravitreal injection of colchicine caused microtubule disruption within the axons of the RNFL in nonhuman primate eyes. This was manifest as a reduction of RNFL birefringence, without alteration of RNFL thickness, suggesting that such discrepancies can be informative about the status of axonal degeneration.