Axonal transport and cytoskeletal changes in the laminar regions after elevated intraocular pressure
Axonal transport and cytoskeletal changes in the laminar regions after elevated intraocular pressure
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DOI：
10.1167/iovs.06-1002
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发表时间：
2007-08-01
影响因子：
4.4
通讯作者：
Yu, Dao-Yi
中科院分区：
文献类型：
--
作者：
Balaratnasingam, Chandrakumar;Morgan, William H.;Yu, Dao-Yi
目的。为了研究急性眼压升高后猪视神经板层前区、筛板和板后区轴突细胞骨架的变化，以及这种变化是否与轴突运输异常相对应。方法：选用6头白色长白猪。左眼眼压升高至40~45 mm Hg，持续6h，右眼眼压维持在10~15 mm Hg之间。在实验开始时，将罗丹明-β-异硫氰酸酯(RITC)注射到每只眼的玻璃体中，以研究轴突运输。安乐死后，摘除视神经，准备进行轴突运输和细胞骨架研究。用抗磷酸化神经丝重(NFHp)、磷酸化非依赖性神经细丝重(NFH)、神经细丝轻(NFL)、神经细丝介质(NFM)、微管和微管相关蛋白(MAP)的抗体研究轴突细胞骨架。结果：高眼压组视神经前板、筛板和近400微米板层后视神经区的RITC轴突运输减少。NFHp、NFM和NFH在高眼压眼的前板、筛板和近侧板层后区域显著减少。在NFL、MAP和微管蛋白染色方面没有发现差异。结论：高眼压导致视神经头部轴突运输和细胞骨架改变。细胞骨架的改变可能导致高眼压时发生的轴突运输异常。
PURPOSE. To investigate the axonal cytoskeleton changes occurring in the prelaminar region, lamina cribrosa, and postlaminar region of the porcine optic nerve after an acute increase in intraocular pressure (IOP) and whether this corresponds with axonal transport abnormalities.METHODS. Six white Landrace pigs were used. The left eye IOP was elevated to 40 to 45 mm Hg for 6 hours, and the right eye IOP was maintained between 10 and 15 mm Hg. Rhodamine-beta-isothiocyanate (RITC) was injected into the vitreous of each eye at the beginning of the experiment, to study axonal transport. After euthanasia, optic nerves were removed and prepared for axonal transport and cytoskeleton studies. Antibodies to phosphorylated neurofilament heavy (NFHp), phosphorylation-independent neurofilament heavy (NFH), neurofilament light (NFL), neurofilament medium (NFM), microtubule, and microtubule-associated protein (MAP) were used to study the axonal cytoskeleton. Montages of confocal microscopy images were quantitatively analyzed to investigate simultaneous changes in optic nerve axonal transport and cytoskeletal proteins in the high-IOP and control eyes.RESULTS. Axonal transport of RITC was reduced in the prelaminar, lamina cribrosa, and proximal 400 mu m of the postlaminar optic nerve regions in the high-IOP eye. NFHp, NFM, and NFH were significantly reduced in the prelaminar, lamina cribrosa, and proximal postlaminar regions in the high-IOP eye. No differences in NFL, MAP, and tubulin staining were detected.CONCLUSIONS. Elevated IOP induced both axonal transport and cytoskeleton changes in the optic nerve head. Changes to the cytoskeleton may contribute to the axonal transport abnormalities that occur in elevated IOP.