Abstract
Purpose :
To determine the effects of whole-body exposure to airborne particulate matter (PM) <10 µm in diameter on the susceptibility of C57BL/6 mouse cornea to Pseudomonas aeruginosa (PA) infection and if SKQ1 is protective.
Methods :
Mice were treated topically with PBS or SKQ1 (7.5 μM) 3 times the day before exposure began and once daily before each chamber exposure. Control (air) or PM10 exposure was carried out for 3h/day with concentrations of PM10 averaging 0.5 -1.0 mg/m3. After exposure, corneas were infected with PA 19660. Infection severity was documented by clinical score, slit lamp, PMN quantitation, bacterial plate count, RT-PCR and Western blot. A second set of experiments used SKQ1 with Moxifloxacin to test its potential as an adjunctive treatment to antibiotic therapy.
Results :
The corneas of PBS treated PM10 exposed mice were no different at 1 day postinfection (p.i.) but exhibited earlier perforation/corneal thinning (clinical score of +3/+4) compared to PBS treated control mice at 3 days p.i. Clinical score was unchanged after SKQ1 treatment. After infection, PM10 exposed mice significantly increased mRNA levels in cornea for TNFα, IL-1β, CXCL2, TLR2, TLR4, COX2, and iNOS and significantly decreased mRNA levels for IL-10, NQO1, GR1, and GPX4 over the control group. SKQ1 reversed these effects in both infected PM10 exposed and control mice. Western blots run for TNFα, IL-1β, CXCL2, and GPX4 confirmed the PCR results. PM10 exposure resulted in significantly higher viable bacterial plate counts at 1 and 3 days p.i. SKQ1 had no effect on plate counts in the control air exposed group, but significantly reduced plate counts in PM10 exposed mice at 3 days p.i. There were no significant differences seen in MPO between groups at 1 day p.i., but PM10 exposure significantly increased MPO in corneas at 3 days p.i. and SKQ1 treatment reduced MPO in the PM10 exposed group. SKQ1 was tested as an adjunctive treatment to Moxifloxacin, and although both agents reduced plate count and MPO, addition of SKQ1 was not significantly different from Moxifloxacin treatment alone.
Conclusions :
Whole-body exposure to PM10 increased susceptibility of C57BL/6 to PA infection and SKQ1 significantly reversed the effect of PM10 on proinflammatory cytokines and oxidative stress markers as well as reducing viable bacterial plate counts and MPO, but was not effective as an adjunctive treatment combined with Moxifloxacin.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.