Anders Fabian, Mann Carolina, Liu Aiwei, Teister Julia, Funke Sebastian, Thanos Solon, Grus Franz, Pfeiffer Norbert, Prokosch Verena
a Experimental Ophthalmology, Department of Ophthalmology , University Medical Center of the Johannes Gutenberg University Mainz , Mainz , Germany.
b Department of Experimental Ophthalmology, School of Medicine , University of Münster , Münster , Germany.
Curr Eye Res. 2018 Oct;43(10):1267-1273. doi: 10.1080/02713683.2018.1485950. Epub 2018 Jul 27.
Glaucoma is one of the leading causes of blindness worldwide with age being an important risk factor. However, the pathogenesis remains poorly understood. Aim of this study was to focus on age-dependent molecular changes in an experimental animal model of glaucoma.
Intraocular pressure was elevated in Sprague-Dawley rats aged 3, 14, and 47 weeks for a period of 7 weeks by episcleral vein cauterization. Ganglion cell loss was monitored by an immunohistochemical staining of the Brain-specific homeobox/POU (Pit-1, Oct-2, Unc-86) domain protein 3A positive cells in retinal flat-mounts and spectral-domain optical coherence tomography measuring the retinal nerve fiber layer thickness. Molecular protein alterations were analyzed using a comprehensive mass spectrometric proteomics approach of the retina and vitreous body.
While juvenile animals did not show a significant loss of retinal ganglion cells due to intraocular pressure elevation, adolescent animals showed a decrease up to 26% (p < 0.05). A shift of retinal crystallin protein expression levels within all protein-family subclasses (α, β, γ) could be observed in the youngest animal group (p < 0.05), while the upregulation of crystallin proteins in older animals was less striking. In addition, numerous crystallin proteins were also detected in the vitreous body.
These results provide insights of a potential correlation of age-related glaucomatous damage and the absence of crystallin proteins in the retina.
青光眼是全球主要致盲原因之一，年龄是一个重要的风险因素。然而，其发病机制仍知之甚少。本研究的目的是聚焦于青光眼实验动物模型中与年龄相关的分子变化。
通过烧灼巩膜静脉，使3周龄、14周龄和47周龄的Sprague-Dawley大鼠眼压升高7周。通过视网膜平铺标本中脑特异性同源框/POU（Pit-1、Oct-2、Unc-86）结构域蛋白3A阳性细胞的免疫组织化学染色以及测量视网膜神经纤维层厚度的光谱域光学相干断层扫描来监测神经节细胞损失。使用视网膜和玻璃体的综合质谱蛋白质组学方法分析分子蛋白改变。
虽然幼年动物未因眼压升高而出现明显的视网膜神经节细胞损失，但青春期动物的神经节细胞损失高达26%（p < 0.05）。在最年轻的动物组中，可观察到所有蛋白质家族亚类（α、β、γ）中视网膜晶状体蛋白表达水平的变化（p < 0.05），而老年动物中晶状体蛋白的上调则不太明显。此外，在玻璃体中也检测到了许多晶状体蛋白。
这些结果为年龄相关性青光眼损伤与视网膜中晶状体蛋白缺失之间的潜在关联提供了见解。
