Abstract
Purpose :
The retinal pigment epithelium (RPE) serves as an outer blood retinal barrier during Klebsiella pneumoniae (KP) infection in endogenous endophthalmitis. Nevertheless, the pathogen-associated molecular patterns and the specific adhesion molecules used of RPE cells upon interaction with KP are yet been reported. In this study, we investigate the changes of diabetic ocular environment facilitate the development of KP invasion to the eye.
Methods :
In this study, we investigated the ability of KP to invade human RPE cells (ARPE-19) in in vitro diabetic condition (in 27.5mM and 17.5mM glucose culture medium). Adhesion and invasion assays were undertaken to investigate roles of tight junction proteins, adhesion molecules, acute inflammatory molecules (IL-1, IL-6, IL8) and molecules involved in the pathogen-associated molecular patterns via ELISA and western blot studies. The results were validated via RNA sequencing on ARPE-19 cells.
Results :
We concluded that KP adhesion and invasion to RPE were increased in hyperglycemic condition via breaking down specific tight junction pathway proteins and enhancing specific adhesion molecules including vascular cell adhesion protein 1 (VCAM-1) and activated leukocyte cell adhesion molecule (ALCAM). Furthermore, toll-like receptor 4 (TLR4) was enhanced for pattern recognition and NF-kB and MAPK pathway were involved during KP infection.
Conclusions :
This is the first study to highlight the pattern recognition, adhesion molecules engaged, and signal transduction pathway during KP invasion to the eye in diabetic ocular condition in vitro. The results suggest a strong rationale for between endogenous endophthalmitis and systemic KP infection for individuals with diabetes mellitus.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.