Experimental scleral cross-linking increases glaucoma damage in a mouse model.

Experimental scleral cross-linking increases glaucoma damage in a mouse model.
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DOI:
10.1016/j.exer.2014.08.016
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发表时间:
2014-11
影响因子:
3.4
通讯作者:
Quigley, Harry A.
Quigley, Harry A.
中科院分区:
医学3区
文献类型:
--
作者:
Kimball, Elizabeth C.;Nguyen, Cathy;Steinhart, Matthew R.;Nguyen, Thao D.;Pease, Mary E.;Oglesby, Ericka N.;Oveson, Brian C.;Quigley, Harry A.

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这项研究的目的是评估巩膜交联剂对小鼠青光眼损伤易感性的影响。CD1小鼠在1周内结膜下注射0.5M甘油醛(GA)3次,然后注射微珠引起眼压升高。用酶联免疫吸附试验(ELISA)测定交联度,用光漂白后荧光恢复法(FRAP)测定巩膜通透性,用充气试验测定GA暴露的机械效应。在两个单独的青光眼实验中,对照组小鼠分别注射缓冲注射或不注射。Tonolab法监测眼压,组织学轴突计数法检测视网膜神经节细胞(RGC)丢失。为了排除GA的不良影响,我们进行了视网膜电描记术和详细的视网膜组织学检查。GA暴露对RGC数目、视网膜结构或功能均无明显影响,无论是组织学还是电生理学。在ELISA法中,GA使巩膜的交联度增加了37%,降低了巩膜通透性(FRAP,p=0.001),并在体外充气试验中产生了更陡峭的压力-应变行为。在两个实验性青光眼实验中,在控制眼压随时间变化的水平的情况下,经GA处理的眼在眼压升高时较缓冲液注射眼或对照眼有更大的视网膜节细胞轴突丢失(P=0.049和P=0.01%,多元回归分析)。这是首次报道通过交联性实验改变巩膜,增加小鼠对RGC损伤的易感性。
The purpose of this study was to assess the effect of a scleral cross-linking agent on susceptibility to glaucoma damage in a mouse model. CD1 mice underwent 3 subconjunctival injections of 0.5 M glyceraldehyde (GA) in 1 week, then had elevated intraocular pressure (IOP) induced by bead injection. Degree of cross-linking was measured by enzyme-linked immunosorbent assay (ELISA), scleral permeability was measured by fluorescence recovery after photobleaching (FRAP), and the mechanical effects of GA exposure were measured by inflation testing. Control mice had buffer injection or no injection in 2 separate glaucoma experiments. IOP was monitored by Tonolab and retinal ganglion cell (RGC) loss was measured by histological axon counting. To rule out undesirable effects of GA, we performed electroretinography and detailed histology of the retina. GA exposure had no detectable effects on RGC number, retinal structure or function either histologically or electrophysiologically. GA increased cross-linking of sclera by 37% in an ELISA assay, decreased scleral permeability (FRAP, p = 0.001), and produced a steeper pressure—strain behavior by in vitro inflation testing. In two experimental glaucoma experiments, GA-treated eyes had greater RGC axon loss from elevated IOP than either buffer-injected or control eyes, controlling for level of IOP exposure over time (p = 0.01, and 0.049, multivariable regression analyses). This is the first report that experimental alteration of the sclera, by cross-linking, increases susceptibility to RGC damage in mice.
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