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Targeting RPE Senescence Via Suppressing IL-6/IL-6R Signaling for Treating Retinal Degenerative Diseases.

Tian Zhou1,2, Ziqi Yang1,2, Biyan Ni1,2

  • 1State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, People's Republic of China.

Investigative Ophthalmology & Visual Science
|September 19, 2025
PubMed
Summary
This summary is machine-generated.

Interleukin-6 (IL-6) signaling drives retinal pigment epithelium (RPE) cell senescence and degeneration. Inhibiting IL-6 or its receptor (IL-6R) with tocilizumab rescues senescent RPE cells and protects against retinal degeneration.

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Area of Science:

  • Ophthalmology
  • Cellular Biology
  • Immunology

Background:

  • Progressive retinal pigment epithelium (RPE) cell dysfunction is a key driver of retinal degeneration and blindness.
  • Cellular senescence and inflammation in RPE cells are hallmarks of retinal degeneration, but underlying mechanisms are not fully understood.

Purpose of the Study:

  • To investigate if the IL-6/IL-6R axis induces RPE cell senescence.
  • To evaluate the therapeutic potential of inhibiting this axis in RPE senescence and retinal degeneration.

Main Methods:

  • Established sodium iodate-induced retinal degeneration mouse models.
  • Administered IL-6 neutralizing antibody or tocilizumab (IL-6R inhibitor).
  • Assessed RPE senescence, retinal structure, and function using molecular and imaging techniques.

Main Results:

  • RPE senescence was observed in NaIO₃-induced degeneration, dependent on the IL-6/IL-6R axis.
  • IL-6 exacerbated RPE senescence and retinal degeneration; IL-6 inhibition promoted recovery.
  • STAT3 activation was crucial for IL-6-induced RPE senescence; tocilizumab blocked this pathway.

Conclusions:

  • The IL-6/IL-6R/STAT3 pathway is critical for RPE senescence.
  • Tocilizumab demonstrates therapeutic potential for treating retinal degenerative diseases by mitigating RPE senescence.