Host antimicrobial peptide S100A12 disrupts the fungal membrane by direct binding and inhibits growth and biofilm formation of Fusarium species.

Fungal keratitis is the foremost cause of corneal infections worldwide, of which Fusariumspp. is the common etiological agent that causes loss of vision and warrants surgical intervention. An increase in resistance to the available drugs along with severe side effects of the existing antifungals demands for new effective antimycotics. Here, we demonstrate that antimicrobial peptide S100A12 directly binds to the phospholipids of the fungal membrane, disrupts the structural integrity, and induces generation of reactive oxygen species in fungus. In addition, it inhibits biofilm formation by Fusariumspp. and exhibits antifungal property against Fusariumspp. both in vitro and in vivo. Taken together, our results delve into specific effect of S100A12 against Fusariumspp. with an aim to investigate new antifungal compounds to combat fungal keratitis.

Alternative Therapeutic Interventions: Antimicrobial Peptides and Small Molecules to Treat Microbial Keratitis.

Microbial keratitis is a leading cause of blindness worldwide and results in unilateral vision loss in an estimated 2 million people per year. Bacteria and fungus are two main etiological agents that cause corneal ulcers. Although antibiotics and antifungals are commonly used to treat corneal infections, a clear trend with increasing resistance to these antimicrobials is emerging at rapid pace. Extensive research has been carried out to determine alternative therapeutic interventions, and antimicrobial peptides (AMPs) are increasingly recognized for their clinical potential in treating infections. Small molecules targeted against virulence factors of the pathogens and natural compounds are also explored to meet the challenges and growing demand for therapeutic agents. Here we review the potential of AMPs, small molecules, and natural compounds as alternative therapeutic interventions for the treatment of corneal infections to combat antimicrobial resistance. Additionally, we have also discussed about the different formats of drug delivery systems for optimal administration of drugs to treat microbial keratitis.

Determination of Oxidative Stress Markers in the Aqueous Humor and Corneal Tissues of Patients With Congenital Hereditary Endothelial Dystrophy.

PURPOSE: The aim of this study is to determine the presence of oxidative stress markers in the aqueous humor (AH) and corneal tissues of patients with congenital hereditary endothelial dystrophy (CHED). METHODS: Interventional prospective study was undertaken to quantify levels of ascorbic acid and glutathione in the AH of patients with CHED. AH was collected from patients undergoing keratoplasty and levels of ascorbic acid and glutathione were determined using biochemical assays and measured spectrophotometrically. AH collected from pediatric patients with cataract were used as control. Corneal sections of patients who underwent penetrating keratoplasty were obtained, and presence of glutathione peroxidase 1, catalase, and superoxide dismutase was determined by immunohistochemistry. Tissue sections obtained from cadaveric corneas unsuitable for clinical transplant were used as control. RESULTS: Significantly increased ascorbic acid levels were determined in patients with CHED (605.6 ± 158.9 µM) compared with those in controls (190.5 ± 74.72 µM). However, a trend toward reduced level of glutathione was detected in patients with CHED compared with that in the controls. Increased glutathione peroxidase 1 staining and reduced expression of catalase was detected in corneal tissues of patients with CHED compared with those in control corneal tissues. There was no apparent changes observed in the expression of superoxide dismutase in the corneal sections obtained from patients with CHED. CONCLUSIONS: To the best of our knowledge, this is the first study to determine the levels of ascorbic acid and glutathione in AH of patients with CHED. Our data suggest the presence of oxidative stress in CHED that might be responsible for the pathological changes in patients with CHED.