Fullerol rescues the light-induced retinal damage by modulating Müller glia cell fate
Zhe Cha,
Zhiyuan Yin,
Luodan A,
Lingling Ge,
Junling Yang,
Xiaona Huang,
Hui Gao,
Xia Chen,
Zhou Feng,
Lingyue Mo,
Juncai He,
Shuang Zhu,
Maoru Zhao,
Zui Tao,
Zhanjun Gu,
Haiwei Xu
Affiliations
Zhe Cha
Southwest Eye Hospital, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China; Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Southwest Eye Hospital, Southwest Hospital, Chongqing 400038, China
Zhiyuan Yin
Southwest Eye Hospital, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China; Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Southwest Eye Hospital, Southwest Hospital, Chongqing 400038, China
Luodan A
Southwest Eye Hospital, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China; Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Southwest Eye Hospital, Southwest Hospital, Chongqing 400038, China
Lingling Ge
Southwest Eye Hospital, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China; Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Southwest Eye Hospital, Southwest Hospital, Chongqing 400038, China
Junling Yang
Southwest Eye Hospital, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China; Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Southwest Eye Hospital, Southwest Hospital, Chongqing 400038, China
Xiaona Huang
Southwest Eye Hospital, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China; Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Southwest Eye Hospital, Southwest Hospital, Chongqing 400038, China
Hui Gao
Southwest Eye Hospital, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China; Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Southwest Eye Hospital, Southwest Hospital, Chongqing 400038, China
Xia Chen
Southwest Eye Hospital, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China; Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Southwest Eye Hospital, Southwest Hospital, Chongqing 400038, China
Zhou Feng
Southwest Eye Hospital, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China; Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Southwest Eye Hospital, Southwest Hospital, Chongqing 400038, China
Lingyue Mo
Southwest Eye Hospital, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China; Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Southwest Eye Hospital, Southwest Hospital, Chongqing 400038, China
Juncai He
Southwest Eye Hospital, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China; Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Southwest Eye Hospital, Southwest Hospital, Chongqing 400038, China; Joint Logistics Support Force of Chinese PLA, No. 927 Hospital, Puer 665000, Yunnan, China
Shuang Zhu
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience, Institute of High Energy Physics and National Center for Nanoscience and Technology, Chinese Academy of Sciences, Beijing, 100049, China; College of Materials Science and Optoelectronic Technology, University of Chinese Academy of Sciences, Beijing, 100049, China
Maoru Zhao
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience, Institute of High Energy Physics and National Center for Nanoscience and Technology, Chinese Academy of Sciences, Beijing, 100049, China; College of Materials Science and Optoelectronic Technology, University of Chinese Academy of Sciences, Beijing, 100049, China
Zui Tao
Southwest Eye Hospital, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China; Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Southwest Eye Hospital, Southwest Hospital, Chongqing 400038, China; Corresponding author. Southwest Eye Hospital, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China.
Zhanjun Gu
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience, Institute of High Energy Physics and National Center for Nanoscience and Technology, Chinese Academy of Sciences, Beijing, 100049, China; College of Materials Science and Optoelectronic Technology, University of Chinese Academy of Sciences, Beijing, 100049, China; Corresponding author. CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience, Institute of High Energy Physics and National Center for Nanoscience and Technology, Chinese Academy of Sciences, Beijing, 100049, China.
Haiwei Xu
Southwest Eye Hospital, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China; Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Southwest Eye Hospital, Southwest Hospital, Chongqing 400038, China; Corresponding author. Southwest Eye Hospital, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China.
Excessive light exposure can damage photoreceptors and lead to blindness. Oxidative stress serves a key role in photo-induced retinal damage. Free radical scavengers have been proven to protect against photo-damaged retinal degeneration. Fullerol, a potent antioxidant, has the potential to protect against ultraviolet-B (UVB)-induced cornea injury by activating the endogenous stem cells. However, its effects on cell fate determination of Müller glia (MG) between gliosis and de-differentiation remain unclear. Therefore, we established a MG lineage-tracing mouse model of light-induced retinal damage to examine the therapeutic effects of fullerol. Fullerol exhibited superior protection against light-induced retinal injury compared to glutathione (GSH) and reduced oxidative stress levels, inhibited gliosis by suppressing the TGF-β pathway, and enhanced the de-differentiation of MG cells. RNA sequencing revealed that transcription candidate pathways, including Nrf2 and Wnt10a pathways, were involved in fullerol-induced neuroprotection. Fullerol-mediated transcriptional changes were validated by qPCR, Western blotting, and immunostaining using mouse retinas and human-derived Müller cell lines MIO-M1 cells, confirming that fullerol possibly modulated the Nrf2, Wnt10a, and TGF-β pathways in MG, which suppressed gliosis and promoted the de-differentiation of MG in light-induced retinal degeneration, indicating its potential in treating retinal diseases.
