Activation of Master Autophagy Regulator TFEB During Systemic LPS Administration in the Cornea

Abstract

The involvement of autophagy in the cornea during the systemic inflammatory response elicited by intravenous administration of lipopolysaccharide (LPS) was investigated. Eight-week-old male Sprague-Dawley rats were injected i.v. with 15 mg/kg body weight LPS. RC4 rabbit corneal keratocytes were also used and treated with 100 ng/mL of tumor necrosis factor α (TNFα) and/or cycloheximide (CHX). The nuclear translocation of transcription factor EB (TFEB), the master transcriptional regulator for autophagy, was observed after LPS administration in the corneal epithelium. Induction of autophagy-related proteins was observed in the cornea after LPS administration, as well as in RC4 cells after treatment with TNFα. Administration of trehalose, an inducer of TFEB, mitigated RC4 cell death caused by TNFα/CHX. These results demonstrate the importance of TFEB activation in cellular defense against the systemic inflammatory response in the cornea.