Abstract
Purpose :
Tissue injury causes the stress hormone catecholamine secretion and increases susceptibility to opportunistic infection. Here we explored the effects of inhibiting catecholamone receptor (adrenoceptor) activity on the severity of Pseudomonas aeruginosa (PA) keratitis in mice.
Methods :
Adult C57BL/6 mice were infected with 105 colony forming units (CFU) of PA strain 19660 after central cornea scarified. Corneal catecholamine content was measured. The adrenoceptor antagonist phentolamine (α1+α2), atenolol (β1), ICI118551 (β2) or Timolol (β1+β2) were applied topically 6 h post inoculation and continued every 2 h for 3 days, normal saline (0.9% NaCl) was used as vehicle control. Corneal disease was scored at 1, 2 and 3 days postinfection (dpi). Polymorphonuclear neutrophils (PMN) were evaluated by immunofluorescence staining and myoloperoxidase (MPO) assay. The number of viable bacteria was determined by plate counts. The expressions of mouse inflammation cytokines and PA-virulence factors were measured by real-time qPCR.
Results :
Corneal catecholamine content was increased with the scarring injury. Compared with vehicle and other adrenoceptor antagonists, the β2 adrenoceptor antagonist ICI118551 showed the most significant reduction of corneal disease scores. During the 3 days of observation periods, the corneas maintained the clarity in the mice given with ICI118551, in comparison of perforation in control mice. The number of infiltrated PMN was decreased with the reduced MPO activity in cornea. The corneal bacterial load was reduced from 6 h postinfection and assumed 50% reduction at 1 dpi when compared with vehicle control. Moreover, topical application of ICI118551 down-regulated the expression of mouse IL-1β and TNF-α and PA-virulence factors.
Conclusions :
β2 adrenoceptor inhibition reduces the severity of PA keratitis in mice, representing the potential therapeutic approach to control PA keratitis combined with antibiotics.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.