Abstract
Presentation Description :
The corneal epithelium is a stratified epithelial sheet that protects the cornea from invading pathogens and forms a smooth refractive surface that is essential for vision. As an external mucosal barrier, the corneal epithelium is chronically exposed to many different types of stress, including hyperosmolar and dessicating stress in dry eye disease, hyperglycemic stress in diabetes, and chronic inflammatory stress, among others. Given their role in energy production, mitochondria play a key role in the cellular response to stress. As such, mitochondrial dysfunction is a hallmark of many disease conditions. Using a combination of in vitro cell culture and in vivo animal models, we investigated the metabolic and mitochondrial response to stress in the corneal epithelium. Specifically, we have found that: (1) cells differentially regulate oxygen consumption and spare respiratory capacity, the latter being a key mediator of a cell’s ability to respond to stress; (2) spare respiratory capacity is decreased in response to hyperosmolar and hyperglycemic stress, but is increased in response to IL-1b-mediated inflammation; (3) PTEN-inducible kinase 1 (PINK1)- and receptor mediated mitophagic pathways are temporally and spatially activated in a stress-specific dependent manner. Taken together, these findings have important implications in the maintenance of corneal epithelial homeostasis and the pathophysiology of disease.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.