Alleviation of Photoreceptor Degeneration Based on Fullerenols in rd1 Mice by Reversing Mitochondrial Dysfunction via Modulation of Mitochondrial DNA Transcription and Leakage
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
Search for more papers by this authorXia 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
Search for more papers by this authorLuodan 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
Search for more papers by this authorHui 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
Search for more papers by this authorMaoru 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
Search for more papers by this authorLingling 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
Search for more papers by this authorMinghui Li
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
Search for more papers by this authorCao 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
Search for more papers by this authorCorresponding Author
Yu Gong
Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Southwest Eye Hospital, Southwest Hospital, Chongqing, 400038 China
Department of Ophthalmology, Medical Sciences Research Center, University-Town Hospital of Chongqing Medical University, Chongqing, 400038 China
E-mail: [email protected]; [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
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
E-mail: [email protected]; [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
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
E-mail: [email protected]; [email protected]; [email protected]
Search for more papers by this authorJunling 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
Search for more papers by this authorXia 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
Search for more papers by this authorLuodan 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
Search for more papers by this authorHui 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
Search for more papers by this authorMaoru 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
Search for more papers by this authorLingling 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
Search for more papers by this authorMinghui Li
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
Search for more papers by this authorCao 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
Search for more papers by this authorCorresponding Author
Yu Gong
Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Southwest Eye Hospital, Southwest Hospital, Chongqing, 400038 China
Department of Ophthalmology, Medical Sciences Research Center, University-Town Hospital of Chongqing Medical University, Chongqing, 400038 China
E-mail: [email protected]; [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
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
E-mail: [email protected]; [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
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
E-mail: [email protected]; [email protected]; [email protected]
Search for more papers by this authorAbstract
Poor therapeutic outcomes of antioxidants in ophthalmologic clinical applications, including glutathione during photoreceptor degeneration in retinitis pigmentosa (RP), are caused by limited anti-oxidative capacity. In this study, fullerenols are synthesized and proven to be highly efficient in vitro radical scavengers. Fullerenol-based intravitreal injections significantly improve the flash electroretinogram and light/dark transition tests performed for 28 days on rd1 mice, reduce the thinning of retinal outer nuclear layers, and preserve the Rhodopsin, Gnat-1, and Arrestin expressions of photoreceptors. RNA-sequencing, RT-qPCR, and Western blotting validate that mitochondrial DNA (mt-DNA)-encoded genes of the electron transport chain (ETC), such as mt-Nd4l, mt-Co1, mt-Cytb, and mt-Atp6, are drastically downregulated in the retinas of rd1 mice, whereas nuclear DNA (n-DNA)-encoded genes, such as Ndufa1 and Atp5g3, are abnormally upregulated. Fullerenols thoroughly reverse the abnormal mt-DNA and n-DNA expression patterns of the ETC and restore mitochondrial function in degenerating photoreceptors. Additionally, fullerenols simultaneously repress Flap endonuclease 1 (FEN1)-mediated mt-DNA cleavage and mt-DNA leakage via voltage-dependent anion channel (VDAC) pores by downregulating the transcription of Fen1 and Vdac1, thereby inactivating the downstream pro-inflammatory cGAS-STING pathway. These findings demonstrate that fullerenols can effectively alleviate photoreceptor degeneration in rd1 mice and serve as a viable treatment for RP.
Conflict of Interest
The authors declare no conflict of interest.
Open Research
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Supporting Information
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