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.

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