Evaluation of Spatially Targeted Scleral Stiffening on Neuroprotection in a Rat Model of Glaucoma.
Evaluation of Spatially Targeted Scleral Stiffening on Neuroprotection in a Rat Model of Glaucoma.
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DOI：
10.1167/tvst.11.5.7
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发表时间：
2022-05-02
影响因子：
3
通讯作者：
Ethier, C. Ross
中科院分区：
文献类型：
--
作者：
Gerberich, Brandon G.;Hannon, Bailey G.;Brown, Dillon M.;Read, A. Thomas;Ritch, Matthew D.;Echeverri, Elisa Schrader;Nichols, Lauren;Potnis, Cahil;Sridhar, Sreesh;Toothman, Maya G.;Schwaner, Stephen A.;Winger, Erin J.;Huang, Hannah;Gershon, Gabby S.;Feola, Andrew J.;Pardue, Machelle T.;Prausnitz, Mark R.;Ethier, C. Ross
巩膜硬化可以防止青光眼视网膜神经节细胞（RGC）丢失或与高眼压相关的功能障碍。在这里，我们评估了两种治疗方法的潜在神经保护作用，这两种治疗方法设计为在青光眼实验模型中覆盖整个后巩膜或仅覆盖与视乳头周围巩膜相邻的巩膜。使用京尼平（交联整个后巩膜）或区域选择性光敏剂亚甲蓝（仅硬化视神经周围的视乳头旁区域）在体内硬化大鼠巩膜。使用递送到前房的磁性微珠诱导高眼压。形态和功能的结果，包括视神经轴突计数和外观，视网膜厚度测量的光学相干断层扫描，optomotor的反应，和视网膜电图的痕迹，进行了评估。局部（视乳头周围）和全球（整个后）巩膜硬化治疗成功地增加巩膜硬度，但既没有提供明显的神经保护高血压的眼睛RGC轴突计数和外观，视动反应，或视网膜电图评估。有一个弱的迹象表明，巩膜交联保护视网膜变薄的光学相干断层扫描评估。巩膜硬化在高眼压大鼠中没有表现出神经保护作用。我们假设，缺乏益处可能部分是由于与巩膜硬化剂本身相关的RGC损失（京尼平的情况下为轻度，亚甲蓝的情况下为中度），否定了巩膜硬化的任何潜在益处。巩膜硬化作为神经保护治疗的发展将需要确定更好的耐受性硬化方案和进一步的临床前试验。
Scleral stiffening may protect against glaucomatous retinal ganglion cell (RGC) loss or dysfunction associated with ocular hypertension. Here, we assess the potential neuroprotective effects of two treatments designed to stiffen either the entire posterior sclera or only the sclera adjacent to the peripapillary sclera in an experimental model of glaucoma. Rat sclerae were stiffened in vivo using either genipin (crosslinking the entire posterior sclera) or a regionally selective photosensitizer, methylene blue (stiffening only the juxtaperipapillary region surrounding the optic nerve). Ocular hypertension was induced using magnetic microbeads delivered to the anterior chamber. Morphological and functional outcomes, including optic nerve axon count and appearance, retinal thickness measured by optical coherence tomography, optomotor response, and electroretinography traces, were assessed. Both local (juxtaperipapillary) and global (whole posterior) scleral stiffening treatments were successful at increasing scleral stiffness, but neither provided demonstrable neuroprotection in hypertensive eyes as assessed by RGC axon counts and appearance, optomotor response, or electroretinography. There was a weak indication that scleral crosslinking protected against retinal thinning as assessed by optical coherence tomography. Scleral stiffening was not demonstrated to be neuroprotective in ocular hypertensive rats. We hypothesize that the absence of benefit may in part be due to RGC loss associated with the scleral stiffening agents themselves (mild in the case of genipin, and moderate in the case of methylene blue), negating any potential benefit of scleral stiffening. The development of scleral stiffening as a neuroprotective treatment will require the identification of better tolerated stiffening protocols and further preclinical testing.
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青光眼中的视网膜神经节细胞凋亡与眼内压和IOP诱导的细胞外基质有关。
影响因子：
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13.7
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通讯作者：
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