Abstract
Dry eye is a common ocular inflammatory disorder characterized by tear film instability and reduced tear production. There is increasing evidence that homeostasis of the ocular surface is impacted by the intestinal microbiome. We are interested in investigating the potential role of microbially produced small molecules in mediating the interaction between the intestinal microbiota and the ocular surface. One such molecule is butyrate, a short-chain fatty acid (SCFA) produced by certain members of the gut microbiota through fermentation of dietary fiber. Here we show that SCFA transporter SLC5A8 is expressed in vivo in murine conjunctival and corneal epithelium. Pre-treatment of in vitro corneal epithelial cultures or bone marrow-derived dendritic cells (BMDCs) with phenylbutyrate (PBA) reduces lipopolysaccharide-induced pro-inflammatory Tnf expression. Corneal epithelial cultures and BMDCs isolated from Slc5a8 knockout mice are unable to respond to PBA pre-treatment, suggesting that SLC5A8 is required for the protective effect of PBA. The treatment of mice undergoing desiccating stress (DS) with oral tributyrin, a prodrug form of butyrate, reduces inflammation at the ocular surface in vivo, and this effect partially requires SLC5A8. Finally, expression analysis on conjunctival tissue isolated from mice subjected to DS with and without tributyrin treatment revealed that treatment downregulated genes involved in Type I interferon signaling. Together these data support our hypothesis that SCFAs produced in the gut participate in the maintenance of ocular surface homeostasis.
Highlights
Dry eye is a common ocular inflammatory disorder characterized by tear film instability and reduced tear production
We examined whether short-chain fatty acid (SCFA) could act directly on ocular surface tissue by testing for expression of transporter mRNA in corneal epithelium and conjunctival tissue in the mouse using quantitative digital polymerase chain reaction (PCR)
We looked for expression of the transporter protein in corneal and conjunctival epithelium
Summary
Dry eye is a common ocular inflammatory disorder characterized by tear film instability and reduced tear production. We are interested in investigating the potential role of microbially produced small molecules in mediating the interaction between the intestinal microbiota and the ocular surface One such molecule is butyrate, a short-chain fatty acid (SCFA) produced by certain members of the gut microbiota through fermentation of dietary fiber. Pre-treatment of in vitro corneal epithelial cultures or bone marrow-derived dendritic cells (BMDCs) with phenylbutyrate (PBA) reduces lipopolysaccharide-induced pro-inflammatory Tnf expression. Expression analysis on conjunctival tissue isolated from mice subjected to DS with and without tributyrin treatment revealed that treatment downregulated genes involved in Type I interferon signaling. Together these data support our hypothesis that SCFAs produced in the gut participate in the maintenance of ocular surface homeostasis. This can cause sight threatening corneal epithelial disease and ulceration
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