Fleischer Amelie B, Amann Barbara, von Toerne Christine, Degroote Roxane L, Schmalen Adrian, Weißer Tanja, Hauck Stefanie M, Deeg Cornelia A
Chair of Physiology, Department of Veterinary Sciences, LMU Munich, D-82152 Martinsried, Germany.
Metabolomics and Proteomics Core, Helmholtz Center Munich, German Research Center for Environmental Health, D-80939 Munich, Germany.
Biomolecules. 2025 Feb 14;15(2):288. doi: 10.3390/biom15020288.
Retinal Müller glial cells (RMG) play a crucial role in retinal neuroinflammation, including autoimmune uveitis. Increasing evidence supports their function as active modulators of immune responses and potential atypical antigen-presenting cells (APCs). To further investigate this hypothesis, we conducted a differential proteome analysis of primary equine RMG from healthy controls and horses with equine recurrent uveitis (ERU), a spontaneous model of autoimmune uveitis. This analysis identified 310 proteins with differential abundance. Among these, the Major Histocompatibility Complex (MHC) class II and the enzyme Arginase 1 (ARG1) were significantly enriched in RMG from uveitis-affected horses, whereas Mannose Receptor C-type 2 (MRC2) and its interactor Thrombospondin 1 (THBS1) were more abundant in healthy RMG. The detection of MHC class II in equine RMG, consistent with previous studies, validates the robustness of our approach. Furthermore, the identification of ARG1 and MRC2, together with THBS1, provides new insights into the immunomodulatory and antigen-presenting properties of RMG. Immunohistochemical analyses confirmed the proteomic findings and revealed the spatial distribution of ARG1 and MRC2. ARG1 and MRC2 are thus markers for RMG in the neuroinflammatory or physiological milieu and highlight potential differences in the immune function of RMG, particularly in antigen presentation.
视网膜穆勒胶质细胞（RMG）在包括自身免疫性葡萄膜炎在内的视网膜神经炎症中起关键作用。越来越多的证据支持它们作为免疫反应的活性调节剂和潜在的非典型抗原呈递细胞（APC）的功能。为了进一步研究这一假设，我们对来自健康对照马和患有马反复性葡萄膜炎（ERU，一种自身免疫性葡萄膜炎的自发模型）的马的原代RMG进行了差异蛋白质组分析。该分析鉴定出310种丰度有差异的蛋白质。其中，主要组织相容性复合体（MHC）II类和精氨酸酶1（ARG1）在受葡萄膜炎影响的马的RMG中显著富集，而甘露糖受体C型2（MRC2）及其相互作用蛋白血小板反应蛋白1（THBS1）在健康的RMG中更为丰富。与先前的研究一致，在马RMG中检测到MHC II类证实了我们方法的稳健性。此外，ARG1、MRC2以及THBS1的鉴定为RMG的免疫调节和抗原呈递特性提供了新的见解。免疫组织化学分析证实了蛋白质组学的发现，并揭示了ARG1和MRC2的空间分布。因此，ARG1和MRC2是神经炎症或生理环境中RMG的标志物，并突出了RMG免疫功能的潜在差异，特别是在抗原呈递方面。
