Department of Pharmacy, Center for Drug Research, Ludwig-Maximilians-Universität München, Munich, 81377, Germany.
Bioinformatics Unit, Biomedical Center Munich, Ludwig-Maximilians-Universität München, Planegg-Martinsried, 82152, Germany.
J Neuroinflammation. 2024 Aug 2;21(1):190. doi: 10.1186/s12974-024-03175-8.
Retinitis pigmentosa (RP), an inherited retinal disease, affects 1,5 million people worldwide. The initial mutation-driven photoreceptor degeneration leads to chronic inflammation, characterized by Müller cell activation and upregulation of CD44. CD44 is a cell surface transmembrane glycoprotein and the primary receptor for hyaluronic acid. It is involved in many pathological processes, but little is known about CD44's retinal functions. CD44 expression is also increased in Müller cells from our Pde6b RP mouse model. To gain a more detailed understanding of CD44's role in healthy and diseased retinas, we analyzed Cd44 and Cd44Pde6b mice, respectively. The loss of CD44 led to enhanced photoreceptor degeneration, reduced retinal function, and increased inflammatory response. To understand the underlying mechanism, we performed proteomic analysis on isolated Müller cells from Cd44 and Cd44Pde6b retinas and identified a significant downregulation of glutamate transporter 1 (SLC1A2). This downregulation was accompanied by higher glutamate levels, suggesting impaired glutamate homeostasis. These novel findings indicate that CD44 stimulates glutamate uptake via SLC1A2 in Müller cells, which in turn, supports photoreceptor survival and function.
色素性视网膜炎（RP）是一种遗传性视网膜疾病，影响全球 150 万人。最初的突变驱动的感光细胞变性导致慢性炎症，其特征是 Müller 细胞激活和 CD44 上调。CD44 是一种细胞表面跨膜糖蛋白，是透明质酸的主要受体。它参与许多病理过程，但对 CD44 的视网膜功能知之甚少。我们的 Pde6b RP 小鼠模型中 Müller 细胞中的 CD44 表达也增加了。为了更详细地了解 CD44 在健康和患病视网膜中的作用，我们分别分析了 Cd44 和 Cd44Pde6b 小鼠。CD44 的缺失导致感光细胞变性增强、视网膜功能降低和炎症反应增加。为了了解潜在的机制，我们对从 Cd44 和 Cd44Pde6b 视网膜中分离出的 Müller 细胞进行了蛋白质组学分析，发现谷氨酸转运蛋白 1（SLC1A2）显著下调。这种下调伴随着谷氨酸水平的升高，表明谷氨酸稳态受损。这些新发现表明，CD44 通过 Müller 细胞中的 SLC1A2 刺激谷氨酸摄取，进而支持感光细胞的存活和功能。
