Host Immune Response and Associated Clinical Features in a Primary Cytomegalovirus Eye Infection Model Using Anterior Chamber Inoculation

Invest Ophthalmol Vis Sci. 2022 May 2;63(5):18. doi: 10.1167/iovs.63.5.18.

Abstract

Purpose: To investigate the pathogenesis of cytomegalovirus (CMV)-associated anterior segment infection in immunocompetent hosts and evaluate the effects of ganciclovir and glucocorticoid treatment in management of the disease.

Methods: We used an inoculation model to reproduce CMV anterior segment infection in immunocompetent rats. Flow cytometry, cytokine analysis, histopathological sections, and quantitative polymerase chain reaction were performed to investigate the immune response after CMV infection. The effects of ganciclovir and glucocorticoid treatment were also assessed.

Results: Anterior chamber inoculation of CMV in rats provoked characteristic pathological features of human CMV anterior segment infection. The innate and adaptive immunity sequentially developed in an anterior segment after inoculation, and the elevation of intraocular pressure (IOP) was highly associated with ocular infiltration and inflammation. Early ocular immune response reduced virus DNA in the anterior segment and alleviated viral lymphadenopathy. Early intervention with ganciclovir enhanced the release of cytokines associated with T response and facilitated recruitment of NKT and T cells in drainage lymph nodes. Glucocorticoid treatment, alone or combined with ganciclovir, decreased elevation of IOP but also impeded DNA clearance.

Conclusions: The inoculation model reproduced characteristic pathological features of human CMV anterior segment infection. The use of glucocorticoid in current practice may hinder viral clearance, and ganciclovir therapy can assist cytokine expression to combat the virus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anterior Chamber / pathology
  • Antiviral Agents / therapeutic use
  • Aqueous Humor
  • Cytokines
  • Cytomegalovirus / genetics
  • Cytomegalovirus Infections*
  • DNA, Viral / analysis
  • Eye Infections*
  • Eye Infections, Viral* / diagnosis
  • Eye Infections, Viral* / drug therapy
  • Eye Infections, Viral* / pathology
  • Ganciclovir / therapeutic use
  • Glucocorticoids / therapeutic use
  • Immunity
  • Rats

Substances

  • Antiviral Agents
  • Cytokines
  • DNA, Viral
  • Glucocorticoids
  • Ganciclovir