Inflammation in dry eye diseases culminating in loss of ocular homeostasis

Abstract

This article describes recent advances in the principles of dry eye diseases, with a strong focus on the autoimmune-mediated disease, Sjögren’s syndrome. The lacrimal functional unit, comprised of the lacrimal glands, the meibomian glands, components of the ocular surface, as well as the connecting sensory and motor neurons, is not merely a target of inflammation and autoimmunity in response to glandular injury or perturbations, but an integral player in the development and onset of disease. To better understand the molecular and cellular mechanisms involved in dry eye syndromes, animal models that mimic individual or multiple clinical manifestations of the human disease have been developed and studied. Although an increasing number of CD4⁺ T-helper cell populations are being identified as critical components in the pathogenesis of dry eye conditions, recent studies have defined the importance of B lymphocytes in both the preclinical and clinical phases of the disease process. Furthermore, data are accumulating that indicate that lymphocytes infiltrating the lacrimal functional unit are recruited by chemokines secreted by macrophages and dendritic cells that enter the glands first. Decreased lacrimation appears to be the result of a complex set of sequential molecular and pathological processes, yet the actual underlying causes remain unknown and a challenge to identify. Here, we present a discussion on the complexity of how immune cell populations and their interactions with the lacrimal functional unit may be involved in orchestrating dysfunctional lacrimation.

Keywords::

• dry eye disease
• lacrimal gland
• lymphocytic foci
• meibomian gland
• ocular surface
• Sjögren’s syndrome
• tear film

Financial & competing interests disclosure

The authors are recipients of PHS grants K99 DE018958 (Cuong Q Nguyen), DE014344 and AI081952 (Ammon B Peck) from the NIH, and funds from the Center for Orphaned Autoimmune Diseases, University of Florida, Gainesville, Florida, USA. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.