Abstract
Purpose :
To examine the relationship between autophagic responses and intraocular inflammation, in the endotoxin-induced uveitis (EIU) model of autophagy-deficient mice in which AMBRA1, an important molecule for autophagic response, is deleted in a drug-dependent manner (AMBRA1-KO mice).
Methods :
We administered tamoxifen to AMBRA1F/FxRosa-Cre-ER2-Tg and control AMBRA1F/F mice to prepare the mice in which Ambra1 gene is knocked-out in whole-body tissues in a drug-dependent manner and corresponding control mice. The EIU models were prepared by intraperitoneally administering lipopolysaccharide to both. After collecting the retina, the transcripts of inflammatory cytokines, TNF-α, MCP-1, and IL-6, were determined by quantitative PCR (qPCR). In immunohistochemistry, autophagic responses were evaluated by staining the autophagic markers, Beclin1 and LC-3.
Results :
In the qPCR analysis, the expression levels of TNF-α and MCP-1 in the retina were significantly higher in the AMBRA1-KO mice than those in the control mice by 1.33 and 8.76 folds, respectively, whereas no difference was found in that of IL-6. Immunohistochemical staining showed lower expression of Beclin1 and LC-3 in the retinal inner plexiform layer in AMBRA1-KO mice compared to those in control mice.
Conclusions :
In the AMBRA1-KO mice, we observed increases in some inflammatory cytokines in the retina and decreases of the autophagic responses in their retinal inner plexiform layer compared to those in the control mice. Thus, our results suggest the exacerbation of inflammation due to the reduction of autophagic responses in the retina.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.