Abstract
Purpose :
The aim of this study is to evaluate the clinical and histological changes which are associated with the reformulated DA-6034(AJU-S56/GLH8NDE) in the cornea, conjunctiva and lacrimal glands from a dry eye mouse model and to compare its efficacy with those of commercial drugs, diquafosol(DQS) and rebamipide(REB)
Methods :
The dry eye animal model, using the NOD.B10.H2b mouse, was induced with scopolamine hydrobromide injection and under the desiccation stress(less than 40%RH) for 10 days. After 10 days, the mice were instilled with vehicle, DA-6034 and REB four times a day, or DA-6034 and DQS six times a day for 21 days. For the clinical analysis, the assessments of tear production, corneal irregularity and fluorescence staining were performed at 3rd, 7th, 10th, 14th, and 21th day. For the histologic analysis, the orbit and lacrimal glands of mice were excised at 21th day and corneal epithelial cell detachment, conjunctival goblet cell and mucin density were respectively assessed by hematoxylin-eosin staining, periodic acid Schiff and mucin staining. Also, the expression levels of inflammatory factors, were assessed by immunohistochemical examinations using the lacrimal glands.
Results :
Tear production and corneal epithelial cell detachment showed significant improvement after treatment with DA-6034 (P < 0.05) which could be comparable with those of DQS and REB, Also, the corneal irregularity with DA-6034 showed significant improvement and the results were significantly better than those from DQS(P < 0.05) and similar to those from REB. Corneal fluorescence staining with DA-6034 was significantly decreased (P < 0.05) and similar to that with REB. The density of conjunctival goblet cells and mucin with DA-6034 showed significant increase and better efficacy than DQS and REB (P < 0.05). The expression levels of TNF-α, MMP-9, IL-1β, IL-6, and NF-κB with DA-6034 were significantly decreased (P < 0.05) and the results were similar to those from REB.
Conclusions :
Reformulated DA-6034 induced more mucin secretion than those of DQS or REB . Also it indicated remarkably superior anti-inflammatory effects to DQS. These caused the improvement of tear production and corneal irregularity in the dry eye mouse. These results suggested that DA-6034 could be a practical therapeutic candidate for ocular epithelial recovery through mucin and tear secretion, goblet cell proliferation, and anti-inflammation effect.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.