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

Abstract

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.

Clinical Features and Treatment Outcomes of Carbapenem-Resistant Pseudomonas aeruginosa Keratitis

“…Phage therapy has proven effective against the management of P aeruginosa keratitis, yet its use is strain specific. Additionally, development of antiseptics and antimicrobial peptides are warranted for these recalcitrant pathogens …”

Antimicrobial activity of cell-free supernatant derived from Ligilactobacillus animalis SWLA-1 in a novel ex vivo canine corneal infection model

“…aureus and plays a major role in staphylococcal keratitis ( 33 , 34 ). The destruction and lysis of corneal structures induced by bacterial infection increase corneal opacity with the presence of opaque or cloudy area on the cornea ( 35 ). The change in corneal opacity and the measurement of bacterial growth using CFU was determined in this study.…”

Differential expression of antimicrobial peptides in human fungal keratitis

“…Compared with existing antibacterial agents, AMPs have unique mode of action, so they have received special attention as a potential treatment for microbial infections [26] . As numerous studies over the past two decades have shown, human AMPs already play a crucial role in microbial keratitis [11,[15][16][17][24][25][26] .…”

“…Antimicrobial peptides (AMPs) are host defense protein peptides secreted naturally by epithelial cells and immune cells, playing an important role in the primitive immune system and adaptive immune system, and having a wide range of activities against pathogens such as viruses, bacteria, and fungi [10][11][12][13] . Several articles have described the presence of AMPs, such as human beta-defensin (HBD) and LL-37 on the surface of the human ocular surface (OS) and their expression in corneal infections [14][15][16][17] . In recent years, a large number of studies have confirmed the antifungal activity of AMPs in animals [18][19][20][21] , in corneal epithelial cells [22][23] and in humans [24][25] .…”