SOCS1-Derived Peptide Administered by Eye Drops Prevents Retinal Neuroinflammation and Vascular Leakage in Experimental Diabetes

Int J Mol Sci. 2019 Jul 24;20(15):3615. doi: 10.3390/ijms20153615.

Abstract

Current treatments for diabetic retinopathy (DR) target late stages when vision has already been significantly affected. Accumulating evidence suggests that neuroinflammation plays a major role in the pathogenesis of DR, resulting in the disruption of the blood-retinal barrier. Suppressors of cytokine signaling (SOCS) are cytokine-inducible proteins that function as a negative feedback loop regulating cytokine responses. On this basis, the aim of the present study was to evaluate the effect of a SOCS1-derived peptide administered by eye drops (2 weeks) on retinal neuroinflammation and early microvascular abnormalities in a db/db mouse model. In brief, we found that SOCS1-derived peptide significantly reduced glial activation and neural apoptosis induced by diabetes, as well as retinal levels of proinflammatory cytokines. Moreover, a significant improvement of electroretinogram parameters was observed, thus revealing a clear impact of the histological findings on global retinal function. Finally, SOCS1-derived peptide prevented the disruption of the blood-retinal barrier. Overall, our results suggest that topical administration of SOCS1-derived peptide is effective in preventing retinal neuroinflammation and early microvascular impairment. These findings could open up a new strategy for the treatment of early stages of DR.

Keywords: db/db mouse; diabetic retinopathy; microvascular impairment; neuroinflammation; suppressors of cytokine signaling.

MeSH terms

  • Animals
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetic Retinopathy / drug therapy*
  • Diabetic Retinopathy / genetics
  • Diabetic Retinopathy / pathology
  • Disease Models, Animal
  • Electroretinography
  • Humans
  • Inflammation / drug therapy*
  • Inflammation / genetics
  • Inflammation / pathology
  • Mice
  • Ophthalmic Solutions / pharmacology
  • Peptides / chemistry
  • Peptides / pharmacology
  • Retina / drug effects
  • Retina / pathology
  • Suppressor of Cytokine Signaling 1 Protein / chemistry
  • Suppressor of Cytokine Signaling 1 Protein / pharmacology*

Substances

  • Ophthalmic Solutions
  • Peptides
  • Suppressor of Cytokine Signaling 1 Protein