Preclinical study of a new matrix to help the ocular surface in dry eye disease.

Dry eye disease (DED), a multifactorial disease of the tears and ocular system, causes loss of tear film homeostasis with damage to the ocular surface. This study aimed to assess whether a peculiar matrix based on sodium hyaluronate (HA), xanthan gum (XNT), glycine (GLY) and betaine (BET) as osmoprotectants, could be involved in biological responses. Wound healing assay on human corneal epithelial (HCE) cells in monolayer showed a synergistic effect of the combination of HA + XNT (**p ≤ 0.01) together with an efficient extracellular matrix remodeling of the formulation in SkinEthic™ HCE 3D-model sought by integrin beta-1 (ITGß1) expression and morphological analysis by hematoxylin and eosin (H&E), compared to a reference marketed product. The synergistic effect of HA + XNT + GLY + BET showed an antioxidant effect on HCE cells (***p ≤ 0.001). Real-time PCR analysis showed that the combination of GLY + BET seemed to ameliorate the effect exhibited by the single osmoprotectants in reducing tumor necrosis factor-alpha (TNFα, #p ≤ 0.05), interleukin-1 beta (IL1ß, ####p ≤ 0.0001) and cyclooxygenases-2 (COX2, ####p ≤ 0.0001) genes in SIRC cells under hyperosmotic stress. Furthermore, pretreatment with XNT, alone and in combination (##p ≤ 0.01), reduced COX2 expression in human non-small cell lung cancer cells (A549). Finally, the formulation was well-tolerated following q.i.d. ocular administration in rabbits during a 28-day study. Due to the synergistic effect of its components, the matrix proved able to repair the ocular surface restoring cell homeostasis and to protect the ocular surface from pro-inflammatory pathways activation and oxidative damage, thus behaving as a reactive oxygen species (ROS) scavenger.

Effects of a new lipid tear substitute in a mouse model of dry eye.

PURPOSE: The present investigation is aimed to evaluate the effect of a new lipid artificial tear on tear volume and ocular surface signs in a mouse model of dry eye and to test the hypothesis that the combined application with sodium hyaluronate can improve the performance of the treatments. METHODS: A new oil-in-water emulsion, a 0.2% sodium hyaluronate solution, or their combined administration were given to dry eye mice maintained in a controlled environment chamber and treated with scopolamine (0.75-mg transdermal patch). Mice were treated 4 times a day with (a) sodium hyaluronate, (b) emulsion, and (c) sodium hyaluronate followed by emulsion. A control group of mice exposed to controlled environment chamber remained untreated (CTRL+). Tear volume and corneal damage were assessed after 3 and 7 days of treatment by cotton thread test and fluorescein staining. RESULTS: As regards tear volume, sodium hyaluronate did not show a statistically significant effect at either end point; the emulsion was effective after 7 days, whereas their combined administration counteracted the lacrimal decrease induced by the model both at 3 and 7 days. Corneal damage was reduced in all treated groups with respect to CTRL+. This effect was statistically significant after 3 days when the emulsion alone or in combination with sodium hyaluronate was used, while hyaluronate improved this clinical sign after 7 days. CONCLUSIONS: Our data suggest that the new lipid tear substitute can be used to treat clinical signs of dry eye and that the combined administration with hyaluronate can decrease the lag time before the effect, when the evaporative and the aqueous-deficient components are present.