An eye drop combination for the treatment of Staphylococcus aureus-induced keratitis in Rats. Repurposing ibuprofen

Background: infectious keratitis is a life-hindering disease that has been one of the leading causes of blindness worldwide for decades, the use of antibiotics and/or anti-inflammatory drugs is of crucial importance in improving the outcome and preventing the sequelae. The current study aimed at testing a combination of levofloxacin and ibuprofen in the treatment of Staphylococcus aureus-associated keratitis with special emphasis on the probable antimicrobial and antibiofilm capacities of NSAID moiety. Methods: keratitis was induced in male Sprague Dawley rats by abrasion in the right eyes after topical anesthesia and then the wounded eyes were inoculated with a 10 µl aliquot containing Staphylococcus aureus. Rats were divided into five groups: keratitis, infected keratitis rats, infected keratitis rats treated with 0.5% levofloxacin, infected keratitis rats treated with 0.3% ibuprofen, and infected keratitis rats treated with 0.5% levofloxacin+0.3% ibuprofen. Treatments were given as eye drops. After two weeks of treatment, the corneal tissues were isolated and examined by using hematoxylin-eosin staining and RT-PCR. Results: the molecular study showed that rats treated with combined eye therapy of 0.5% levofloxacin+0.3% ibuprofen had corneas with the lowest expression levels of inflammatory mediators; interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), and toll-like receptor 4 (TLR4), metalloproteinases (proteolytic enzymes capable of degrading extracellular matrix between corneal cells), corneal angiogenesis; vascular endothelial growth factor A (VEGF-A) and proapoptotic BCL2 associated X (Bax) compared to other groups. Histological corneal tissue investigation proved the molecular results, that disclosed promoting corneal wound healing, reducing angiogenesis and inflammation in the rats' group treated with levofloxacin+ibuprofen combined therapy compared with the use of individual eye therapy. Conclusions: thus, combined eye therapy of levofloxacin+ibuprofen could be promising in the management of bacterial keratitis and repair the damage caused by inflammation and ocular neovascularization.