The role of SOCS3/pSTAT3 pathway in the development of diabetic retinopathy

Research output: Contribution to conferenceAbstractpeer-review

Abstract

Purpose: Suppressor of cytokine signalling (SOCS) proteins are feedback inhibitors of the JAK/STAT pathway. SOCS3 critically controls STAT3 activation, cytokine signalling and inflammatory gene expression in macrophages and microglia. In this study, we investigated the role of SOCS3/STAT3 in myeloid cells in the initiation and progression of diabetic retinopathy (DR). 
Methods: Mice with a conditional deletion of SOCS3 in myeloid cells (LysMCre-SOCS3 fl/fl) and C57BL/6J (as control) were rendered diabetic by a low-dose multiple intraperitoneal injections of Stroptozocine. Diabetes related retinal changes, including leukostasis, acellular capilliaries, and microglial activation were assessed at different stages of disease. Bone marrow derived macrophages (BMDMs) from LysMCreSOCS3 fl/fl and C57BL/6J mice were cultured in high glucose (HG) medium, and cell activation was evaluated by real-time RT-PCR.
Results: In C57BL/6J diabetic mice the expression of phosphorylated STAT3 (pSTAT3) was increased and SOCS3 was decreased in the retina. Interleukin 6 (IL-6), the main cytokine that stimulates STAT3 activation, was increased in the plamsa in diabetic mice. Although blood glucose levels and Hbac-1 were comparable between LysMCre-SOCS3fl/fl and WT mice after STZ injection, the LysMCreSOCS3 fl/fl diabetic mice developed severe retinal vasculopathy, including increased leukostasis and microglial activation at one month and enhanced acellular capillary formation at 6 months after diabetes induction. 
Conclusions: our study suggests that the JAK/STAT3 pathway is involved in the initiation and progression of DR, and uncontrolled STAT3 activation results in accelerated DR progression. Targeting the STAT3 pathway may be a novel approach for the management of DR.
Original languageEnglish
Publication statusPublished - 07 May 2015
EventARVO ( the Association for Research in Vision and Ophthalmology) 2015 Annual Meeting - Denver, United States
Duration: 03 May 201507 May 2015

Conference

ConferenceARVO ( the Association for Research in Vision and Ophthalmology) 2015 Annual Meeting
CountryUnited States
CityDenver
Period03/05/201507/05/2015

Bibliographical note

Program number 5849

Fingerprint Dive into the research topics of 'The role of SOCS3/pSTAT3 pathway in the development of diabetic retinopathy'. Together they form a unique fingerprint.

Cite this