Ythdf2 Ablation Protects Aged Retina From RGC Dendrite Shrinking and Visual Decline

Aging Cell. 2025 Jul;24(7):e70107. doi: 10.1111/acel.70107. Epub 2025 May 15.

Abstract

Aging-related retinal degeneration and vision loss have been severely affecting the elderly worldwide. Previously, we showed that the m6A reader YTHDF2 is a negative regulator for dendrite development and protection of retinal ganglion cells (RGC) in mice. Here, we further show that conditional ablation of Ythdf2 protects the retina from RGC dendrite shrinking and vision loss in aged mice. Additionally, we identify Hspa12a and Islr2 as the potential YTHDF2 target mRNAs mediating these effects. Together, our results indicate that the m6A reader YTHDF2 regulates retinal degeneration caused by aging, which might provide important therapeutic potential for developing new treatment approaches against aging-related vision loss.

Keywords: YTHDF2; aging; dendrite; m6A; retinal degeneration; visual acuity.

MeSH terms

  • Aging*
  • Animals
  • Dendrites* / metabolism
  • Dendrites* / pathology
  • Mice
  • Mice, Inbred C57BL
  • RNA-Binding Proteins* / genetics
  • RNA-Binding Proteins* / metabolism
  • Retina* / metabolism
  • Retina* / pathology
  • Retinal Degeneration* / genetics
  • Retinal Degeneration* / metabolism
  • Retinal Degeneration* / pathology
  • Retinal Ganglion Cells* / metabolism
  • Retinal Ganglion Cells* / pathology

Substances

  • RNA-Binding Proteins