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Who Pays the Toll for Solving the Enigma of Corneal Herpes?

Hayashi, Kozaburo MD, PhD*; Hooper, Laura C. PhD*; Shimomura, Yoshikazu MD, PhD

Cornea:
doi: 10.1097/ICO.0b013e3182a2dfc5
Article
Abstract

Abstract: In herpetic stromal keratitis (HSK), herpes simplex virus type-1 DNA fragments and herpes simplex virus-immunoglobulin G immune complexes are present in corneas long after the infective virus has disappeared. These viral components are highly immunogenic and potentiate the production of proinflammatory cytokines and chemokines via Toll-like receptors expressed on corneal cells and macrophages. In addition, angiogenic factors, such as the vascular endothelium growth factor and the tissue-damaging enzyme, matrix metalloproteinase 9, are induced by corneal cells and macrophages through the recognition of these viral components in the pathogenesis of HSK. Upon neovascularization, robust infiltration of leukocytes via leaky new vessels is elicited. Activated polymorphonuclear leukocytes (PMNs) secrete hydrogen peroxide and myeloperoxidase, which inhibit viral growth. PMNs also produce tumor necrosis factor, monokine-induced by interferon-γ (CXCL9), and nitric oxide. These factors provide a local environment that can induce the differentiation of peripheral CD4+ T cells to induce Th1-predominant immunopathology. Thus, strategies developed to alter these pathways should lead to new preventative and therapeutic measures for the treatment of HSK.

Author Information

*Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD; and

Department of Ophthalmology, School of Medicine, Kinki University, Osaka, Japan.

Reprints: Kozaburo Hayashi, 1-26-8 Chofugaoka, Chofu, Tokyo 182-0021, Japan (e-mail: kozaburo@yc4.so-net.ne.jp).

The authors have no funding or conflicts of interest to disclose.

Received June 18, 2013

Accepted June 28, 2013

© 2013 by Lippincott Williams & Wilkins.