More than Antibiotics: Latest Therapeutics in the Treatment and Prevention of Ocular Surface Infections

Abstract

Ocular surface infections have been common issues for ophthalmologists for decades. Traditional strategies for infection include antibiotics, antiviral agents, and steroids. However, multiple drug-resistant bacteria have become more common with the prevalence of antibiotic use. Furthermore, an ideal treatment for an infectious disease should not only emphasize eliminating the microorganism but also maintaining clear and satisfying visual acuity. Immunogenetic inflammation, tissue fibrosis, and corneal scarring pose serious threats to vision, and they are not attenuated or prevented by traditional antimicrobial therapeutics. Herein, we collected information about current management techniques including stem-cell therapy, probiotics, and gene therapy as well as preventive strategies related to Toll-like receptors. Finally, we will introduce the latest research findings in ocular drug-delivery systems, which may enhance the bioavailability and efficiency of ocular therapeutics. The clinical application of improved delivery systems and novel therapeutics may support people suffering from ocular surface infections.

Keywords: ocular drug delivery systems; ocular surface infection; probiotics; siRNA therapy; stem cell therapy.

Figure 1

Each Toll-like receptor has its own function. The TLR1/2 complex recognizes the triacylated lipoprotein commonly found in Gram-negative bacteria, and the TLR2/6 complex recognizes the diacylated lipoprotein synthesized by Gram-positive bacteria [35,36,37]. LPS serves as a specific ligand for TLR4, and flagellin can bind to TLR5 [38]. With regard to TLRs located on the endosomal membrane, TLR3 recognizes dsDNA [39], and both TLR7 and TLR8 can recognize ssRNA [40]. TLR9 can bind to CpG-containing DNA [41]. Activated TLRs then trigger a downstream cascade and contribute to antimicrobial effects.

Figure 2

(A) MSCs can migrate to a site of inflammation and differentiate into tissue-specific cells for repair. (B) MSCs inhibit the expression of MMP-2 and MMP-9, attenuating scar formation. (C) Inhibition of TGF-β1 signaling reduces fibrogenesis. (D) MSC-derived HGF reduces type I and type III collagen fibers, which contribute to scarring. (E) Antimicrobial molecules including LL-37, lipocalin, BD2, and hepcidin secreted by MSCs can inhibit bacterial growth. (F) IDO, TSG6, IL-6, PGE2, and NO can exert immunomodulation, inhibiting proliferation of T cell, B cells, and natural killer cells and inducing M2 macrophage differentiation. (G) MCP-1, which induces immune-cell infiltration, is inhibited by MSCs. (H) Tolerogenic dendritic cells are enhanced by MSCs.

Figure 3

The regulatory mechanism of siRNA on gene expression. (A) siRNAs pass the cell membrane. (B) siRNAs then load into the RNA-induced silencing complex (RISC), which is part of a family of ribonucleoprotein complexes and is able to locate target mRNAs [111]. (C) RISC selects a strand with a less thermodynamically stable 5’ end and degrades the other strand, known as a passenger strand [112,113,114]. (D) The RISC–siRNA complex binds to the target mRNA. (E) The target mRNA is degraded.