Small Molecule Modulation of the Integrated Stress Response Governs the Keratoconic Phenotype In Vitro.

ABSTRACT:

Purpose

The degenerative corneal disease keratoconus is a leading indicator for corneal transplant with an unknown etiology. We recently identified the activation of the integrated stress response (ISR) in ex vivo human corneas and in vitro cell culture. Utilizing small molecules to modulate the ISR we sought to investigate the effects of stimulating the ISR in healthy cells to recapitulate aspects of the in vitro keratoconic phenotype and whether relieving the ISR signaling would recover the disease phenotype.

Methods

Corneal fibroblasts were extracted from patients undergoing corneal transplant or unaffected cadaverous donor limbal rings. Cells were exposed to the DNA damage-inducible protein (GADD34) inhibitor SAL003 to stimulate the ISR, or Trans-ISRIB to relieve ISR sig

SUBMITTER: Soiberman US 

PROVIDER: S-EPMC6686743 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature