Identification of circular RNA-Dcaf6 as a therapeutic target for optic nerve crush-induced RGC degeneration

Yuke Ji; Jing Li; Sha Liu; Junya Zhu; Jin Yao; Ke-Ran Li; Biao Yan

doi:10.1016/j.ygeno.2023.110776

Identification of circular RNA-Dcaf6 as a therapeutic target for optic nerve crush-induced RGC degeneration

Genomics. 2024 Jan;116(1):110776. doi: 10.1016/j.ygeno.2023.110776. Epub 2023 Dec 30.

Authors

Yuke Ji¹, Jing Li², Sha Liu¹, Junya Zhu¹, Jin Yao³, Ke-Ran Li⁴, Biao Yan⁵

Affiliations

¹ Department of Ophthalmology and Optometry, The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, China; Department of Ophthalmology and Optometry, The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing, China.
² Eye Institute and Department of Ophthalmology, Eye and ENT Hospital, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China.
³ Department of Ophthalmology and Optometry, The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, China; Department of Ophthalmology and Optometry, The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing, China. Electronic address: yaojin@njmu.edu.cn.
⁴ Department of Ophthalmology and Optometry, The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, China; Department of Ophthalmology and Optometry, The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing, China. Electronic address: likeran@njmu.edu.cn.
⁵ Eye Institute and Department of Ophthalmology, Eye and ENT Hospital, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China; NHC Key Laboratory of Myopia Fudan University, Key Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University, Shanghai, China. Electronic address: biao.yan@fdeent.org.

PMID: 38163571
DOI: 10.1016/j.ygeno.2023.110776

Abstract

The death of retinal ganglion cells (RGCs) can cause irreversible injury in visual function. Clarifying the mechanism of RGC degeneration is critical for the development of therapeutic strategies. Circular RNAs (circRNAs) are important regulators in many biological and pathological processes. Herein, we performed circRNA microarrays to identify dysregulated circRNAs following optic nerve crush (ONC). The results showed that 221 circRNAs were differentially expressed between ONC retinas and normal retinas. Notably, the levels of circular RNA-Dcaf6 (cDcaf6) expression in aqueous humor of glaucoma patients were higher than that in cataract patients. cDcaf6 silencing could reduce oxidative stress-induced RGC apoptosis in vitro and alleviate retinal neurodegeneration in vivo as shown by increased neuronal nuclei antigen (NeuN, neuronal bodies) and beta-III-tubulin (TUBB3, neuronal filaments) staining and reduced glial fibrillary acidic protein (GFAP, activated glial cells) and vimentin (activated glial cells) staining. Collectively, this study identifies a promising target for treating retinal neurodegeneration.

Keywords: Circular RNAs; Glaucoma; Optic nerve crush; Retinal degeneration; Retinal ganglion cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Disease Models, Animal
Humans
Optic Nerve / metabolism
Optic Nerve / pathology
Optic Nerve Injuries* / drug therapy
Optic Nerve Injuries* / genetics
Optic Nerve Injuries* / metabolism
RNA, Circular* / genetics
RNA, Circular* / metabolism
Retina
Retinal Ganglion Cells / metabolism
Retinal Ganglion Cells / pathology

Substances

RNA, Circular
DCAF6 protein, human