Pathogenesis of Ocular Infections
Ocular infection can occur via exogenous inoculation or hematogenous seeding, which is rare. The initiation, severity, and characteristics of subsequent infection are influenced by the interplay between the virulence of the pathogen, the inoculum size, and the competence and nature of host defense mechanisms. Microbial virulence factors represent evolutionary adaptations by each microorganism that increase the organism’s odds of infection and survival. For example, highly virulent pathogens are more likely to cause infection than an equal number of less virulent pathogens; however, an infection may still result from either exposure, with the only difference being chance. The status of host defense mechanisms also determines the threshold of inoculum at which infection is more likely to occur. Compromised cells or organisms may not be able to avert infection as well as healthy cells or tissues (see Defense Mechanisms of the External Eye and Cornea in Chapter 1).
In ocular surface infections acquired via exogenous inoculation, adherence of organisms to ocular surface epithelium is the first step. Many microorganisms express adhesins, proteins that bind with high affinity to host cell surface molecules, for example:
Candida albicans expresses surface proteins that mimic mammalian integrins (transmembrane proteins that mediate cell–cell and cell–extracellular matrix interactions).
Viruses typically express surface proteins or glycoproteins that attach to constitutive cell surface molecules such as heparan sulfate (herpes simplex virus) or sialic acid (adenovirus).
Acanthamoeba trophozoites express a mannose-binding protein that attaches to surface epithelial cells.
Few organisms can invade an intact epithelium. Those that can include
Others must rely on a break in epithelial barrier function. For example, microbial proteases facilitate invasion by inducing cell lysis, degrading the extracellular matrix, and activating native corneal matrix–derived metalloproteinases (MMPs), triggering autodigestion. Bacterial exotoxins, such as those produced by streptococci, staphylococci, and Pseudomonas aeruginosa, can induce corneal cell necrosis. Acanthamoeba species and certain fungi secrete collagenases, whereas P aeruginosa elastase and alkaline protease destroy collagen and proteoglycan components of the cornea and degrade immunoglobulins, complement, interleukins, and other inflammatory cytokines. For viruses, adherence interactions facilitate invasion by the appropriation of host cell mechanisms.
Once adherent, some bacteria protect themselves from unfavorable elements of their physical environment, such as immunologic cells or antibacterial molecules in the tears, by the expression of exopolysaccharides organized into a biofilm, a 3-dimensional structure that allows interbacterial communication and signaling that interferes with phagocytosis. For viruses, evasion of the immune response involves multiple strategies.
Most organisms are eventually cleared from the site of an acute infection, but some persist in the host indefinitely. For example, following primary infection, herpes simplex virus and varicella-zoster virus establish latency in trigeminal ganglion cells. Chlamydial organisms survive and cause local chronic disease by persistence within intracellular phagosomes.
McDougald D, Rice SA, Barraud N, Steinberg PD, Kjelleberg S. Should we stay or should we go: mechanisms and ecological consequences for biofilm dispersal. Nat Rev Microbiol. 2011;10(1):39–50.
Momburg F, Hengel H. Corking the bottleneck: the transporter associated with antigen processing as a target for immune subversion by viruses. Curr Top Microbiol Immunol. 2002; 269:57–74.
Excerpted from BCSC 2020-2021 series: Section 10 - Glaucoma. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.