SOCS1-derived peptide administered by eye drops prevents retinal neuroinflammation and vascular leakage in experimental diabetes

Abstract

Diabetic retinopathy; Neuroinflammation; Suppressors of cytokine signaling

Retinopatía diabética; Neuroinflamación; Supresores de señalizadores de citoquinas

Retinopatia diabètica; Neuroinflamació; Supressors de senyalitzadors de citoquines

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.

This study was supported by grants from the Ministerio de Economia y Competitividad (PI16/00541, SAF2015-63696-R, PI14/00386, PI17/01495 and DTS-2017/00203). Cristina Sola-Adell is a recipient of a Predoctoral Research Grant from MINECO (BES-2013-064944). Joel Sampedro is a recipient of a Predoctoral Research Grant from AGAUR.