Abstract
Purpose: :
To evaluate the beneficial effect of trehalose (TT) instillation and to determine whether the disaccharide operates to alleviate ocular surface damages in a dry eye murine model.
Methods: :
Dry eye was induced in mice using the intelligently controlled environmental system (ICES). After 21 days housed in the ICES without topical treatment, mice were randomly divided into three groups: no eye drops (ICES), treated for three weeks, four times a day with PBS 0.01M 10-µl/eye bilaterally (ICES+PBS) or with TT 87.6 mM 10-µl/eye bilaterally (ICES+TT). A mice group was not exposed to ICES andreceived no treatment to be used as a control group (UT). The ocular surface integrity in each group was evaluated using Oregon Green Dextran- (OGD) and fluorescein-staining. The expression/distribution of occludin, involucrin and SPRR-2 were performed by immunohistology analysis on whole mounted corneas. Hsp70 and MMP-9 expressions were estimated by immunohistology on the corneal tissue sections. The ocular surface inflammation associated to each treatment was estimated by the mRNA quantification of IL-1β, IL-2, IL-6, IL-17 and TNF-α in the conjunctiva by RT-PCR.
Results: :
The score of OGD staining by the cornea epithelium was significantly lower in ICES+TT group than in ICES and ICES+PBS groups. The corneal epithelium structure appeared, using occludin staining, markedly more homogenous in ICES+TT than in ICES and ICES+PBS groups and showed no desquamating apical epithelial cells. The labelling of involucrin and SPRR-2 on whole mounted corneas revealed an up-regulation of the expression of these proteins in the groups which received no treatment or PBS instillation compared to the ICES+TT group. The immunolabeling of Hsp70 and MMP-9 on tissue sections revealed a marked increase expression in corneal epithelium in response to ICES. The group treated with trehalose showed a similar profile expression of Hsp70 and MMP-9 than the control group (UT). The level expression of mRNA coding to the proinflammatory cytokines IL-1β, IL-2, IL-6, IL-17 and TNF-α were strongly and significantly lower in the conjunctiva of mice exposed to ICES treated with trehalose than in dry eye mice which received no treatment or PBS instillation.
Conclusions: :
Trehalose application restored the ocular surface integrity in mice with dry eye injuries.
Keywords: cornea: tears/tear film/dry eye • cornea: basic science