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Protective Effect of Raf-1 Kinase Inhibitory Protein on Diabetic Retinal Neurodegeneration through P38-MAPK Pathway

Chuanling Wu1,2, Kai Xu3, Wenqiang Liu4

  • 1Teaching and Research Section of Basic Medicine, Jianhu College, Zhejiang Industry Polytechnic College, Shaoxing, Zhejiang, China.

Current Eye Research
|June 16, 2021
PubMed
Abstract

Insights

Raf-1 kinase inhibitory protein (RKIP) prevents diabetic retinal neurodegeneration by inhibiting the p38-MAPK pathway. RKIP overexpression reduced Müller cell apoptosis and protected against retinal damage in a rat model.

Area of Science:

  • Ophthalmology
  • Neuroscience
  • Molecular Biology

Background:

  • Diabetic retinopathy is a leading cause of vision loss.
  • Neurodegeneration plays a critical role in diabetic retinopathy pathogenesis.
  • Raf-1 kinase inhibitory protein (RKIP) is implicated in cellular stress responses.

Purpose of the Study:

  • To investigate the protective effects of RKIP against diabetic retinal neurodegeneration.
  • To elucidate the role of RKIP in high glucose-induced Müller cell apoptosis.
  • To determine the molecular mechanisms underlying RKIP's action in a diabetic rat model.

Main Methods:

  • Streptozotocin-induced diabetic rat model and high glucose-treated rat Müller cells were used.
  • RKIP gene overexpression was achieved via lentiviral vectors.
  • Western blotting, immunofluorescence, glutamate assays, and flow cytometry were employed to assess molecular changes and apoptosis.

Main Results:

  • High glucose increased Müller cell apoptosis, which was attenuated by RKIP overexpression.
  • In diabetic rats, RKIP overexpression reversed increased p38-MAPK and GFAP expression and reduced caspase-3 levels.
  • RKIP overexpression normalized RKIP, GS, and GLAST expression and decreased retinal glutamate levels.

Conclusions:

  • RKIP gene therapy prevents diabetic retinal neurodegeneration in rats.
  • RKIP likely exerts its protective effects by inhibiting the p38-MAPK signaling pathway.
  • RKIP shows therapeutic potential for managing diabetic retinopathy.
Keywords:
Müller cellsRaf-1 kinase inhibitory proteindiabetic retinal neurodegenerationdiabetic retinopathyintravitreal injectionp38 mitogen-activated protein kinase

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