Purchase this article with an account.
Thomas W Carion, David Kracht, Eliisa Strand, Cody McWhirter, Gabriel Sosne, Elizabeth A Berger; Thymosin Beta-4 and Ciprofloxacin Adjunctive Therapy Improves Pseudomonas aeruginosa Induced Keratitis. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4294.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Pseudomonas aeruginosa (PA) is an opportunistic pathogen that can induce bacterial keratitis, especially in contact lens users. With the increasing incidence of antibiotic resistance and contraindication for corticosteroid use, the goal of this study is to develop an adjunctive therapy that prevents corneal perforation and accelerates wound healing. As such, thymosin beta-4 (Tβ4) is a naturally occurring polypeptide that has been shown to elicit rapid corneal reepithelialization and a reduction in corneal inflammation, which was examined as an adjunct to ciprofloxacin in the current study.
Ocular infection was induced in B6 mice using PA ATCC 19660 (5 μL of 1 x 106 CFU). Mice were treated 3× daily with PBS, Tβ4, Tβ4 + ciprofloxacin or ciprofloxacin alone. Disease outcome was assessed at 3 and 5 days post-infection by clinical score, slit lamp photography and histopathology. Cytokine profile, bacterial load and PMN infiltration were determined by real-time RT-PCR, bacterial plate counts and myeloperoxidase assay, respectively.
Tβ4 treatment alone did not change the disease response compared to PBS control as indicated by clinical score and photographs taken by slit-lamp; however, Tβ4 + ciprofloxacin significantly improved disease outcome compared to PBS, Tβ4 alone and ciprofloxacin alone. This outcome correlated with decreases in pro-inflammatory mediators (TNF-α, IL-1β, MIP-2, iNOS, COX-2, 5-LOX); while anti-inflammatory/pro-resolving protein molecules (TGF-β, 12-LOX, 15-LOX) were enhanced in response to the adjunctive therapy. In addition, mediators of wound healing were up-regulated after Tβ4 + ciprofloxacin treatment. This response was further augmented by a decrease in both bacterial load and PMN infiltration. Further, histological analysis revealed a more intact corneal epithelium with less infiltrating inflammatory cells in Tβ4 + ciprofloxacin-treated corneas when compared to all other treatment groups.
Overall, these data provide evidence that wound healing is an essential component to successful resolution of PA induced ocular infection. Use of Tβ4 as an adjunct to ciprofloxacin may provide a novel, more efficacious clinical treatment for bacterial keratitis by promoting rapid corneal wound healing and suppressing inflammation, while decreasing bacterial load.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
This PDF is available to Subscribers Only