Molecular signaling from microglia impacts macroglia autophagy and neurons survival in glaucoma
Huan Yu1, Huimin Zhong2, Jun Sun1
1Department of Ophthalmology, Ruijin Hospital Affiliated Medical School, Shanghai Jiaotong University, 197 Ruijin Er Road, Shanghai 200025, China.
Abstract:
Interactions between microglia and macroglia play important roles in the neurodegeneration of the central nervous system and so is the situation between microglia and Müller cells in retina neurodegenerations like glaucoma. This study focuses on the roles of microglia-derived osteopontin (OPN) in impacting Müller cells and retinal ganglion cells (RGCs). Rat model and cell pressurization culture were used to simulate glaucoma scenarios. Animals were differently treated with anti-OPN, suppressors of OPN receptors (Itgαvβ3/CD44) or microglia inhibitor minocycline, while isolated retinal Müller cells were accordingly treated with conditioned media from microglia culture pretreated with pressuring, overexpression-OPN, SiR-OPN, or minocycline. SB203580 was introduced to explore the role of p38 MAPK signaling pathway. Results revealed microglia may secret OPN to impact Müller cells' autophagy and RGCs survival via binding to Itgαvβ3/CD44 receptors in glaucomatous neurodegeneration with involvement of p38 MAPK pathway. This discovery may benefit understanding neurodegenerative disorders and exploring therapeutics.
Insights
Microglia-derived osteopontin (OPN) impacts Müller cells and retinal ganglion cells (RGCs) in glaucoma. Targeting OPN and its receptors may offer new therapeutic strategies for neurodegenerative eye diseases.
Area of Science:
- Neuroscience
- Ophthalmology
- Cell Biology
Background:
- Microglia and macroglia interactions are crucial in central nervous system neurodegeneration.
- Similar interactions between microglia and Müller cells are implicated in retinal neurodegenerations, such as glaucoma.
Purpose of the Study:
- To investigate the role of microglia-derived osteopontin (OPN) in Müller cells and retinal ganglion cells (RGCs) in glaucoma.
- To elucidate the underlying molecular mechanisms involving OPN receptors and signaling pathways.
Main Methods:
- Simulated glaucoma using rat models and cell pressurization culture.
- Treated animals and isolated retinal Müller cells with anti-OPN, OPN receptor inhibitors (Itgαvβ3/CD44), minocycline, and conditioned media.
- Utilized SB203580 to explore the p38 MAPK signaling pathway.
Main Results:
- Microglia secrete OPN, which affects Müller cell autophagy and RGC survival in glaucoma.
- OPN exerts its effects by binding to Itgαvβ3/CD44 receptors on Müller cells.
- The p38 MAPK signaling pathway is involved in these OPN-mediated effects.
Conclusions:
- Microglia-derived OPN plays a significant role in glaucomatous neurodegeneration by impacting Müller cells and RGCs.
- Targeting the OPN/Itgαvβ3/CD44 axis and the p38 MAPK pathway presents a potential therapeutic avenue for glaucoma.
- This research enhances understanding of neurodegenerative disorders and informs the development of novel therapeutics.
