Molecular signaling from microglia impacts macroglia autophagy and neurons survival in glaucoma

Huan Yu; Huimin Zhong; Jun Sun; Na Li; Junjue Chen; Bingqiao Shen; Ping Huang; Xi Shen; Shouyue Huang; Yisheng Zhong

doi:10.1016/j.isci.2023.106839

Molecular signaling from microglia impacts macroglia autophagy and neurons survival in glaucoma

iScience. 2023 May 9;26(6):106839. doi: 10.1016/j.isci.2023.106839. eCollection 2023 Jun 16.

Authors

Huan Yu¹, Huimin Zhong², Jun Sun¹, Na Li¹, Junjue Chen¹, Bingqiao Shen¹, Ping Huang³, Xi Shen¹, Shouyue Huang¹, Yisheng Zhong^{1

4}

Affiliations

¹ Department of Ophthalmology, Ruijin Hospital Affiliated Medical School, Shanghai Jiaotong University, 197 Ruijin Er Road, Shanghai 200025, China.
² Department of Ophthalmology, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
³ Department of Orthopaedics, Shanghai Key Laboratory for Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital Affiliated Medical School, Shanghai Jiaotong University, 197 Ruijin Er Road, Shanghai 200025, China.
⁴ Department of Ophthalmology, Zhoushan Branch of Ruijin Hospital Affiliated Medical School, Shanghai Jiaotong University, Zhoushan, 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.

Keywords: Molecular neuroscience; Neuroscience; Sensory neuroscience.