LFA-1/ICAM-1 Interaction as a Therapeutic Target in Dry Eye Disease

J Ocul Pharmacol Ther. Jan/Feb 2017;33(1):5-12. doi: 10.1089/jop.2016.0105. Epub 2016 Dec 1.

Abstract

Dry eye disease (DED) is a common ocular disorder associated with inflammation of the lacrimal gland and ocular surface. The interaction of the integrin lymphocyte function-associated antigen-1 (LFA-1) with its cognate ligand intercellular adhesion molecule-1 (ICAM-1) is known to have important roles in the interaction of a variety of cells involved in immune responses and inflammation, including those prominent in ocular surface inflammation. Lifitegrast, an LFA-1 antagonist that blocks binding of ICAM-1 to LFA-1, has recently been approved in the United States for the treatment of signs and symptoms of DED. In this review, we evaluate research findings to explore the potential role of LFA-1/ICAM-1 interaction in the pathophysiology of DED, and the evidence supporting LFA-1/ICAM-1 interaction as a rational therapeutic target in DED. The results of our review suggest that LFA-1/ICAM-1 interaction may play important roles in the cell-mediated immune response and inflammation associated with DED, including facilitating the homing of dendritic cells to the lymph nodes, interaction of dendritic cells with T cells and subsequent T cell activation/differentiation, migration of activated CD4+ T cells from the lymph nodes to the ocular surface, reactivation of T cells by resident antigen-presenting cells at the ocular surface, and recruitment and retention of LFA-1-expressing T cells in the conjunctival epithelium. Based on the available evidence, inhibition of LFA-1/ICAM-1 interaction represents a rational targeted approach in treating DED. Notably, inhibition of LFA-1/ICAM-1 binding with lifitegrast offers a novel approach to reducing ocular surface inflammation in this condition.

Keywords: ICAM-1; LFA-1; LFA-1 antagonist; dry eye disease; inflammation; lifitegrast.

Publication types

  • Review

MeSH terms

  • Animals
  • Dry Eye Syndromes / drug therapy*
  • Dry Eye Syndromes / metabolism*
  • Dry Eye Syndromes / pathology
  • Humans
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Inflammation / pathology
  • Intercellular Adhesion Molecule-1 / metabolism*
  • Lymphocyte Function-Associated Antigen-1 / metabolism*

Substances

  • Lymphocyte Function-Associated Antigen-1
  • Intercellular Adhesion Molecule-1