Ocular Surface Infection Mediated Molecular Stress Responses: A Review

Abstract

Infection mediated ocular surface stress responses are activated as early defense mechanisms in response to host cell damage. Integrated stress responses initiate the host response to different types of infections and modulate the transcription of key genes and translation of proteins. The crosstalk between host and pathogen results in profound alterations in cellular and molecular homeostasis triggering specific stress responses in the infected tissues. The amplitude and variations of such responses are partly responsible for the disease severity and clinical sequelae. Understanding the etiology and pathogenesis of ocular infections is important for early diagnosis and effective treatment. This review considers the molecular status of infection mediated ocular surface stress responses which may shed light on the importance of the host stress-signaling pathways. In this review, we collated literature on the molecular studies of all ocular surface infections and summarize the results from such studies systematically. Identification of important mediators involved in the crosstalk between the stress response and activation of diverse signaling molecules in host ocular surface infection may provide novel molecular targets for maintaining the cellular homeostasis during infection. These targets can be then explored and validated for diagnostic and therapeutic purposes.

Keywords: bacterial conjunctivitis; bacterial keratitis; fungal conjunctivitis; fungal keratitis; gene expression; host stress response; ocular surface infections; proteins; viral conjunctivitis; viral keratitis.

Figure 1

Schematic representation of changes in ocular tissue in: (A) Conjunctivitis: Inflammation of conjunctiva with infiltration of immune cells (neutrophils, lymphocytes, mast cells) which results in disruption in structure and inflammation leading to clinical symptoms and signs. (B) Keratitis: Infection of the cornea by different pathogens results in formation of a corneal ulcer or infiltrate with disruption in Bowman’s layer, epithelial and stromal edema with presence of inflammatory cells. Severe cases can also have inflammation in the anterior chamber in the form of hypopyon and keratic precipitates on the endothelium. (C) H&E staining of section on the right shows the histopathology of an infected cornea illustrating disruption of the Bowman’s layer and dense infiltration of the stroma by polymorphonuclear cells.

Figure 2

Slit-lamp photographs showing clinical features of different keratitis. (a) Fungal keratitis showing classic feathery margins and hypopyon. (b) Bacterial keratitis showing central dense infiltrate with hypopyon in the anterior chamber. (c) Acanthamoeba keratitis showing ring infiltrate in the cornea. (d) Herpes viral epithelial keratitis showing dendrite stained with fluorescein dye seen under cobalt blue filter. (e) Disciform keratitis shown with slit image of the cornea showing central stromal edema with keratic precipitates on the endothelium. (f) Recurrent herpes viral stromal keratitis with peripheral deep vascularization and central stromal edema and scarring. (g) In vivo confocal microscopy (IVCM) image of a cornea with Acanthamoeba keratitis showing hyperreflective cyst form of acanthamoeba and inflammatory cells (red circles). Panels shown are representative IVCM images with a depth of 31 microns. (h) IVCM image of a cornea with fungal keratitis showing fungal filaments (yellow arrows). Panels shown are representative IVCM images a depth of 320 microns. Confocal images were taken using Rostock Corneal Module/Heidelberg Retina Tomograph II (RCM/HRT2; Heidel Engineering GmBH, Dossenheim, Germany). Scale bar represents 50 µm.

Figure 3

Drug–target interaction network constructed using DrugBank database. Drugs and targets are presented by circles and squares, respectively. Drug–target interactions are represented by the lines connecting related drugs and targets. Green (square) targets represent bacterial infection, blue (square) targets represents viral infection, and red (square) targets represent fungal infection.