First Author | Robinson R | Year | 2022 |
Journal | Sci Rep | Volume | 12 |
Issue | 1 | Pages | 17626 |
PubMed ID | 36271280 | Mgi Jnum | J:333900 |
Mgi Id | MGI:7379803 | Doi | 10.1038/s41598-022-22329-3 |
Citation | Robinson R, et al. (2022) Generation and characterization of a Muller-glial-cell-specific Il6ra knockout mouse to delineate the effects of IL-6 trans-signaling in the retina. Sci Rep 12(1):17626 |
abstractText | 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-6Ralpha); 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-6Ralpha that are thus capable of both classical and trans-signaling. Muller 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. |