Urea and ocular surface: Synthesis, secretion and its role in tear film homeostasis

Urea has been detected in the tear film, aqueous humor, and vitreous of the eye. While most of the urea in the aqueous humor and vitreous is considered to be an ultrafiltrate from the blood vessels, the presence of urea transporters and urea-synthesizing enzymes in the lacrimal gland, meibomian glands, conjunctiva, and cornea suggests ureagenesis occurring at the ocular surface. This review summarizes the distribution and function of urea transporters, urea and its synthesizing enzymes at the ocular surface to analyze their role in the tear film homeostasis. Urea transporters (UT)-A- and UT-B-as well as the enzymes arginase I, II, and agmatinase are located at the ocular surface. Urea concentration on the ocular surface is influenced by blood urea concentration, the amount of urea released by the tear fluid, tear evaporation, and arginase concentration in the tears. There are conflicting reports on the relationship between tear and plasma urea levels though a linear correlation exists between their levels. Urea protects the ocular surface from osmotic stress and is thought to maintain a lipid-water interface in the lamellar phase of the tear film. The reduction of urea levels in the tears of patients with evaporative dry eye suggests its possible role in tear film stability. Other than mitigating osmotic stress, urea has hydrating properties as well. Animal studies have demonstrated the healing effects of urea on the corneal epithelium. Future studies examining the variations in urea content in tears from different ocular surfaces, at different times of day, and under different environmental conditions would further solidify the role of urea in tear film stability.