The effect of 3% diquafosol sodium eye drops on the meibomian gland alterations of the superoxide dismutase-1 knockout mice

Abstract

Purpose : Superoxide dismutase-1 knock out (SOD-1 KO) mouse has been reported to be a model for age related meibomian gland(MG) alterations. We investigated the effect of a two week 3% diquafosol sodium (DQS) eye drop application (6 times/day) on the MGs in the SOD-1 KO mice in comparison to the wild type mice.

Methods : Ten eyes of 5 SOD-1 KO male mice with C57BL/background and 10 eyes of 5 C57BL6 strain wild–type male mice were examined at 50 weeks before and 2 weeks after application of 3 % DQS eye drops. Tear film stability and corneal epithelial damage was evaluated by fluorescein and lissamine green (LG) stainings. Anterior segment photography was carried out before and after eye drop instillations. Aqueous tear quantity was measured with phenol-red-impregnated cotton threads without anesthesia. Animals were sacrificed after eye drop application at 52 weeks and the ocular specimens underwent HE, Oil red O as well as cytokeratin 4 and 13 immunohistochemistry stainings. Quantitative real time-PCR for cytokeratin 4 and 13 mRNA expression was also performed. All studies were performed in accordance with the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research.

Results : The mean pre-treatment fluorescein and LG staining scores were significantly higher and the mean BUT was significantly shorter in the SOD-1 KO mice compared to the WT mice. These scores improved significantly in the SOD-1 KO mice after 2 weeks of DQS treatment (p<0.01). The cytokeratin 4 and 13 staining intensity and the mRNA expressions decreased significantly with 3% DQS treatment (p<0.01). The mean number of secretory lipid droplets in the meibomian glands as quantified with Oil red O staining increased significantly after DQS treatment (p<0.01).

Conclusions : Two week application of 3% DQS eye drops was found to be effective in terms of improvement of meibomian gland keratinization and lipid secretion in the SOD-1 KO mice.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.