# cGAS knockout inhibited endotoxin-induced uveitis in mice

## TL;DR

This study shows that removing the cGAS gene in mice reduces eye inflammation caused by endotoxins, suggesting cGAS could be a new treatment target for uveitis.

## Contribution

The study demonstrates that cGAS knockout inhibits endotoxin-induced uveitis, identifying cGAS as a potential therapeutic target.

## Key findings

- Cgas knockout mice showed reduced vitreous inflammation and retinal vascular leakage.
- Retinal macrophage infiltration and microglial activation were inhibited in Cgas knockout mice.
- cGAS-STING pathway activation was confirmed through RNA sequencing and western blotting.

## Abstract

Our research focused on the impact of the cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)–stimulator of interferon genes (STING) pathway on retinal inflammation and employed an endotoxin-induced uveitis (EIU) model. EIU was provoked in mice through the intravitreal administration of lipopolysaccharide. Transcriptome analysis was performed via bulk RNA sequencing. Cytosolic mitochondrial DNA levels in the retina were quantified via PCR. Western blotting was used to assess the activation of cGAS‒STING signaling at specified times after intravitreal lipopolysaccharide injection. To understand the influence of the cGAS‒STING pathway on inflammatory retinal disorders, Cgas knockout mice were developed. Fundus imaging and fluorescein angiography were conducted to observe vitreous inflammation. Microstructural analysis of the eyes was performed, and histopathological scoring was performed. Retinal leukocytosis assays were used to evaluate retinal inflammation. Analysis of these differentially expressed mRNAs revealed activation of the cGAS‒STING signaling pathway, which was confirmed by western blotting analysis of these proteins. Using Cgas knockout mice, we observed significant inhibition of endotoxin-induced intraocular inflammation, including reduced vitreous inflammation, reduced retinal vascular leakage, decreased leukocyte adhesion, inhibited infiltration and activation of macrophages in the retina, and inhibited microglial activation. These findings suggest that cGAS might be a potential novel therapeutic target for uveitis.