| First Author | Ayten M | Year | 2024 |
| Journal | J Neuroinflammation | Volume | 21 |
| Issue | 1 | Pages | 190 |
| PubMed ID | 39095775 | Mgi Jnum | J:361339 |
| Mgi Id | MGI:7708413 | Doi | 10.1186/s12974-024-03175-8 |
| Citation | Ayten M, et al. (2024) CD44 signaling in Muller cells impacts photoreceptor function and survival in healthy and diseased retinas. J Neuroinflammation 21(1):190 |
| abstractText | 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 Muller 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 Muller cells from our Pde6b(STOP/STOP) RP mouse model. To gain a more detailed understanding of CD44's role in healthy and diseased retinas, we analyzed Cd44(-/-) and Cd44(-/-)Pde6b(STOP/STOP) 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 Muller cells from Cd44(-/-) and Cd44(-/-)Pde6b(STOP/STOP) 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 Muller cells, which in turn, supports photoreceptor survival and function. |
