Reinehr Sabrina, Guntermann Annika, Theile Janine, Benning Lara, Grotegut Pia, Kuehn Sandra, Serschnitzki Bettina, Dick H Burkhard, Marcus Katrin, Joachim Stephanie C, May Caroline
Experimental Eye Research Institute, University Eye Hospital, Ruhr-University Bochum, In der Schornau 23-25, 44892 Bochum, Germany.
Department Functional Proteomics, Medizinisches Proteom-Center, Ruhr-University Bochum, ProDi E2.227, Gesundheitscampus 4, 44780 Bochum, Germany.
Biology (Basel). 2021 Dec 23;11(1):16. doi: 10.3390/biology11010016.
Glaucoma is a neurodegenerative disease that leads to damage of retinal ganglion cells and the optic nerve. Patients display altered antibody profiles and increased antibody titer, e.g., against S100B. To identify the meaning of these antibodies, animals were immunized with S100B. Retinal ganglion cell loss, optic nerve degeneration, and increased glial cell activity were noted. Here, we aimed to gain more insights into the pathophysiology from a proteomic point of view. Hence, rats were immunized with S100B, while controls received sodium chloride. After 7 and 14 days, retinae were analyzed through mass spectrometry and immunohistology. Using data-independent acquisition-based mass spectrometry, we identified more than 1700 proteins on a high confidence level for both study groups, respectively. Of these 1700, 43 proteins were significantly altered in retinae after 7 days and 67 proteins revealed significant alterations at 14 days. For example, α2-macroglobulin was found significantly increased not only by mass spectrometry analysis, but also with immunohistological staining in S100B retinae at 7 and 14 days. All in all, the identified proteins are often associated with the immune system, such as heat shock protein 60. Once more, these data underline the important role of immunological factors in glaucoma pathogenesis.
青光眼是一种神经退行性疾病，会导致视网膜神经节细胞和视神经受损。患者会出现抗体谱改变和抗体滴度升高的情况，例如针对S100B的抗体。为了确定这些抗体的意义，用S100B对动物进行免疫。观察到视网膜神经节细胞丢失、视神经变性以及神经胶质细胞活性增加。在此，我们旨在从蛋白质组学的角度更深入地了解其病理生理学。因此，用S100B对大鼠进行免疫，而对照组接受氯化钠。7天和14天后，通过质谱分析和免疫组织学对视网膜进行分析。使用基于数据非依赖采集的质谱分析，我们分别在高置信度水平上为两个研究组鉴定出1700多种蛋白质。在这1700种蛋白质中，有43种蛋白质在7天后视网膜中发生了显著变化，67种蛋白质在14天时显示出显著变化。例如，不仅通过质谱分析发现α2-巨球蛋白显著增加，而且在7天和14天时，S100B视网膜的免疫组织化学染色也显示其显著增加。总而言之，鉴定出的蛋白质通常与免疫系统有关，如热休克蛋白60。这些数据再次强调了免疫因素在青光眼发病机制中的重要作用。
