Abstract
The tear film, lacrimal glands, corneal and conjunctival epithelia and Meibomian glands work together as a lacrimal functional unit (LFU) to preserve the integrity and function of the ocular surface. The integrity of this unit is necessary for the health and normal function of the eye and visual system. Nervous connections and systemic hormones are well known factors that maintain the homeostasis of the ocular surface. They control the response to internal and external stimuli. Our and others' studies show that immunological mechanisms also play a pivotal role in regulating the ocular surface environment. Our studies demonstrate how anti-inflammatory factors such as the expression of vascular endothelial growth factor receptor-3 (VEGFR-3) in corneal cells, immature corneal resident antigen-presenting cells, and regulatory T cells play an active role in protecting the ocular surface. Dry eye disease (DED) affects millions of people worldwide and negatively influences the quality of life for patients. In its most severe forms, DED may lead to blindness. The etiology and pathogenesis of DED remain largely unclear. Nonetheless, in this review we summarize the role of the disruption of afferent and efferent immunoregulatory mechanisms that are responsible for the chronicity of the disease, its symptoms, and its clinical signs. We illustrate current anti-inflammatory treatments for DED and propose that prevention of the disruption of immunoregulatory mechanisms may represent a promising therapeutic strategy towards controlling ocular surface inflammation.
Highlights
1.1 Impact of dry eye diseaseDry eye disease (DED) is defined as “a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance, and tear film instability with potential damage to the ocular surface, accompanied by increased osmolarity of the tear film and inflammation of the ocular surface” (Dry Eye Workshop, 2007)
Our studies demonstrate how anti-inflammatory factors such as the expression of vascular endothelial growth factor receptor-3 (VEGFR-3) in corneal cells, immature corneal resident antigen-presenting cells, and regulatory T cells play an active role in protecting the ocular surface
Previous studies in ocular surface inflammation (Niederkorn et al, 2006; Siemasko et al, 2008) show that mice depleted of CD4+CD25+forkhead box P3 (Foxp3)+ Tregs develop exacerbated DED
Summary
Dry eye disease (DED) is defined as “a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance, and tear film instability with potential damage to the ocular surface, accompanied by increased osmolarity of the tear film and inflammation of the ocular surface” (Dry Eye Workshop, 2007). There is no definitive therapy for DED and it remains one of the leading causes of patient visits to ophthalmologists and optometrists (Schaumberg et al, 2002). Tens of millions more have less severe forms of the disease. DED significantly affects the quality of life due to symptoms of pain and irritation. Severe forms of the disease are comparable to reported cases of moderate to severe angina (Buchholz et al, 2006), which limits and degrades performance of common vision-related daily activities, such as reading and driving (Miljanovic et al, 2007). Considering the significant impact of DED on the quality of life, the need for a thorough understanding of the pathogenic mechanisms, which determine the chronicity of the disease, is pressing for the development of new effective treatments
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