Generation and characterization of a Müller-glial-cell-specific Il6ra knockout mouse to delineate the effects of IL-6 trans-signaling in the retina

Rebekah Robinson, Joshua Glass, Ashok Sharma, Shruti Sharma

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Interleukin-6 (IL-6) is implicated in various retinal and vascular complications associated with diabetic retinopathy (DR). This cytokine functions through two main modalities: classical signaling, in cells expressing the membrane-bound receptor (IL-6Rα); and trans-signaling, possible in most cells through a soluble form of the receptor (sIL-6R). These pathways are considered to be anti-inflammatory and pro-inflammatory, respectively. Our recent studies in retinal endothelial cells and diabetic mice have shown that inhibiting only IL-6 trans-signaling is sufficient to prevent increased vascular leakage, oxidative stress, and inflammation characteristic of DR. Isolating the specific effects of each signaling pathway, however, remains difficult in cells expressing IL-6Rα that are thus capable of both classical and trans-signaling. Müller glial cells (MGCs), the most abundant retinal macroglial cells, span the entire retinal thickness with vital roles in maintaining retinal homeostasis and regulating the blood-retinal barrier through secreted factors. The specific effects of IL-6 trans-signaling in MGCs remain poorly understood given their responsiveness to both IL-6 signaling modalities. In this study, we addressed these concerns by generating an MGC-specific knockout mouse using Cre-loxP deletion of the Il6ra cytokine-binding region. We assessed transcriptional and translational Il6ra expression to confirm the knockout and characterized the effects of knockout on visual functioning in these mice.

Original languageEnglish (US)
Article number17626
JournalScientific reports
Volume12
Issue number1
DOIs
StatePublished - Dec 2022

ASJC Scopus subject areas

  • General

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