Cell-free fat extract promotes axon regeneration and retinal ganglion cells survival in traumatic optic neuropathy

Yiyu Sun; Di Chen; Tao Dai; Ziyou Yu; Hui Xie; Xiangsheng Wang; Wenjie Zhang

doi:10.3389/fncel.2024.1344853

Cell-free fat extract promotes axon regeneration and retinal ganglion cells survival in traumatic optic neuropathy

Front Cell Neurosci. 2024 Mar 7:18:1344853. doi: 10.3389/fncel.2024.1344853. eCollection 2024.

Authors

Yiyu Sun^#¹, Di Chen^#², Tao Dai¹, Ziyou Yu³, Hui Xie⁴, Xiangsheng Wang⁵, Wenjie Zhang³

Affiliations

¹ Department of Wound Reconstructive Surgery, Tongji Hospital Affiliated to Tongji University, School of Medicine, Tongji University, Shanghai, China.
² Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
³ Shanghai Key Laboratory of Tissue Engineering, Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
⁴ Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
⁵ Department of Plastic and Reconstructive Surgery, Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, Hangzhou, Zhejiang, China.

^# Contributed equally.

Abstract

Injuries to axons within the central nervous system (CNS) pose a substantial clinical challenge due to their limited regenerative capacity. This study investigates the therapeutic potential of Cell-free fat extract (CEFFE) in CNS injury. CEFFE was injected intravitreally after the optic nerve was crushed. Two weeks post-injury, quantification of regenerated axons and survival rates of retinal ganglion cells (RGCs) were performed. Subsequently, comprehensive gene ontology (GO) an-notation elucidated the cellular origins and functional attributes of CEFFE components. Molecular mechanisms underlying CEFFE's therapeutic effects were explored through Western blotting (WB). Additionally, levels of inflammatory factors within CEFFE were determined using enzyme-linked immunosorbent assay (ELISA), and histological staining of microglia was conducted to assess its impact on neuroinflammation. CEFFE demonstrated a significant capacity to promote axon re-generation and enhance RGCs survival. GO annotation revealed the involvement of 146 proteins within CEFFE in axonogenesis and neurogenesis. WB analysis unveiled the multifaceted pathways through which CEFFE exerts its therapeutic effects. Elevated levels of inflammatory factors were detected through ELISA, and CEFFE exhibited a modulatory effect on microglial activation in the retinal tissue following optic nerve crush (ONC). The present study highlights the therapeutic promise of CEFFE in the management of CNS injuries, exemplified by its ability to foster axon regeneration and improve RGCs survival.

Keywords: RGCs survival; axon regeneration; cell-free fat extract; inflammation factors; microglia.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Shanghai Collaborative Innovation Program on Regenerative Medicine and Stem Cell Research (2019CXJQ01), National Natural Science Foundation of China (Grant No. 82002060), Construction Fund of Medical Key Disciplines of Hangzhou (0020200044), Medical and Health Science and Technology Program of Hangzhou (A20220646).