Abstract
Background: Dry eye disease (DED) is a multifactorial disease where ocular surface inflammation and damage play key etiological roles. Purpose: To compare a combination of 3% trehalose (T) and 0.15% hyaluronic acid (HA) (Thealoz duo®, T/HA) with a tear substitute containing 0.001% hydrocortisone (I) and 0.2% HA (Idroflog®, I/HA), with respect to changes on signs and inflammatory markers in a mouse DED model. Methods: Thirty 12-week-old C57BL/6 mice were exposed in a controlled-environment chamber as a desiccating stress model of DED for 35 days. At day 14 (T1), administration of 5 µL T or I in the right eye (RE) or NaCl 0.9% in the left eye (LE) started, twice a day. Animals were sacrificed after 7 (T2), 14 (T3), 21 (T4, endpoint) days from the beginning of treatment. Corneal fluorescein staining ratio (Image J), histological and histochemical assessment of ocular surface tissues (goblet cell GC density and characterization —PAS, Alcian blue pH 2.5, pH 1.0, and MUC4 expression—in the superior and inferior conjunctiva), and levels of inflammatory markers HLA-DR, IL-1β and TNF-α in cornea and conjunctiva were measured. Results: No animal fully recovered from DED signs at the endpoint. Difference between arms was observed at T3 and T4, with T treated eyes showing a higher corneal damage reduction, PAS-positive GC recovery, lower inflammatory marker expression as compared to the I treated ones. Conclusions: Data suggest that 21 days of treatment with T/HA improved signs, GC recovery and inflammatory markers in a DED mouse model, to a greater extent as compared to I/HA. Data suggest that 21 days of treatment with T/HA improved signs, GC recovery and inflammatory markers in a DED mouse model, to a greater extent as compared to I/HA.
Highlights
Dry eye disease (DED) is recognized as a multifactorial chronic inflammatory disorder, which results in symptoms of ocular discomfort, tear film instability and hyperosmolarity, visual disturbance, and in which neurosensory abnormalities play etiological roles [1]
Data from this study showed that the administration of a Trehalose-containing tear substitute in a DED mouse model improved clinical signs, GC recovery and reduced inflammatory markers, suggesting a breaking effect on the cycle
Three weeks of treatment might be considered insufficient to mimic what happens in real life, but the duration of the study was estimated to ethically balance scientific needs and induced animal suffering and pain, which was confirmed by the overall well-being of the animal at any stage, and in agreement with several other studies [26]
Summary
Dry eye disease (DED) is recognized as a multifactorial chronic inflammatory disorder, which results in symptoms of ocular discomfort, tear film instability and hyperosmolarity, visual disturbance, and in which neurosensory abnormalities play etiological roles [1]. DED is one of the most common reasons for seeking medical care across the world [2] and is a growing global public health problem [3] It represents a considerable burden either for the patient, impacting the quality of life [4] and psychological impact of pain [5], as well as for society with direct and indirect costs due to healthcare system charge and loss of work productivity, respectively [6]. Conclusions: Data suggest that 21 days of treatment with T/HA improved signs, GC recovery and inflammatory markers in a DED mouse model, to a greater extent as compared to I/HA. Data suggest that 21 days of treatment with T/HA improved signs, GC recovery and inflammatory markers in a DED mouse model, to a greater extent as compared to I/HA
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