Ocular Glands Become Infected Secondarily to Infectious Keratitis and Play a Role in Corneal Resistance to Infection

J Virol. 2019 Jul 30;93(16):e00314-19. doi: 10.1128/JVI.00314-19. Print 2019 Aug 15.


Ocular glands play a critical role in eye health through the secretion of factors directly onto the ocular surface. The cornea is a normally transparent tissue necessary for visual acuity located in the anterior segment of the eye. Corneal damage can occur during microbial infection of the cornea, resulting in potentially permanent visual deficits. The involvement of ocular glands during corneal infection has been only briefly described. We hypothesized that ocular glands contribute to resistance as an arm of the eye-associated lymphoid tissue and may also be susceptible to infection secondary to microbial keratitis. Utilizing a mouse model of herpes simplex virus 1 (HSV-1) keratitis, we found that infection of corneas resulted in subsequent infection of ocular glands, including harderian glands (HGs) and extraorbital glands. Similarly, infection of corneas with Pseudomonas aeruginosa resulted in secondary infection of ocular glands. A robust immune response, characterized by increased numbers of immune cells and inflammatory mediators, occurred within ocular glands following HSV-1 keratitis. Removal of HGs altered corneal resistance to HSV-1, as measured by increased viral load, decreased corneal edema, and decreased inflammatory cell infiltration. These novel findings suggest that ocular glands are involved in microbial keratitis through their susceptibility to secondary infection and contribution to corneal resistance.IMPORTANCE Microbial keratitis accounts for up to 700,000 clinical visits annually in the United States. The involvement of ocular glands during microbial keratitis is not readily appreciated, and treatment options do not address the consequences of ocular gland dysfunction. The present study shows that ocular glands are susceptible to direct infection by common ocular pathogens, including HSV-1 and Pseudomonas aeruginosa, subsequent to microbial keratitis. Additionally, ocular glands contribute soluble factors that play a role in corneal resistance to HSV-1 and alter viral load, corneal edema, and immune cell infiltration. Further studies are needed to elucidate the mechanisms by which this occurs.

Keywords: Pseudomonas aeruginosa; T cells; cornea; cytokines; eicosanoids; herpes simplex virus; keratitis; lacrimal gland; myeloid cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers
  • Cornea / microbiology*
  • Cornea / pathology
  • Cornea / virology*
  • Cytokines / metabolism
  • Dacryocystitis / diagnosis
  • Dacryocystitis / etiology*
  • Disease Models, Animal
  • Disease Resistance*
  • Disease Susceptibility*
  • Herpesvirus 1, Human / physiology
  • Inflammation Mediators / metabolism
  • Keratitis / complications*
  • Keratitis / etiology*
  • Keratitis / pathology
  • Mice
  • Organ Specificity


  • Biomarkers
  • Cytokines
  • Inflammation Mediators