Effect of Diquafosol Ophthalmic Solution on Airflow-Induced Ocular Surface Disorder in Diabetic Rats

Atsuyoshi Dota, Asuka Sakamoto, Takashi Nagano, Tadahiro Murakami, Takeshi Matsugi, Atsuyoshi Dota, Asuka Sakamoto, Takashi Nagano, Tadahiro Murakami, Takeshi Matsugi

Abstract

Purpose: To examine the effect of 3% diquafosol ophthalmic solution (DQS) on ocular surface disorders in diabetic model rats maintained in a continuous airflow condition.

Methods: Goto-Kakizaki (GK) rats, a spontaneous model of type 2 diabetes, were exposed to constant airflow for 8 weeks. After the establishment of the animal model in this environment, DQS or saline was instilled six times a day into GK rat eyes for 6 weeks. Schirmer's test was performed before and after 6-week instillations. Corneal fluorescein staining was scored at 2-, 4-, and 6-week instillations. Touch thresholds for the cornea were also determined using a Cochet-Bonnet esthesiometer before and after 6-week instillations.

Results: The mean Schirmer's test score after instillation of DQS was twice higher than that recorded for saline alone. DQS significantly decreased corneal staining scores at 4- and 6-week instillations. No changes in touch thresholds were observed before and after 6-week instillations.

Conclusion: These results suggest that DQS improves corneal epithelial damage by stimulating tear secretion without influencing corneal sensation in diabetic keratopathy. Thus, DQS may have potential for treatment of diabetic patients with dry eye.

Keywords: Goto–Kakizaki rat; corneal epithelial damage; diabetic keratopathy; diquafosol ophthalmic solution; tear volume.

Conflict of interest statement

All authors are employees of Santen Pharmaceutical Co. Ltd. The authors report no other conflicts of interest in this work.

© 2020 Dota et al.

Figures

Figure 1
Figure 1
Study design. Abbreviation: DQS, 3% diquafosol tetrasodium ophthalmic solution.
Figure 2
Figure 2
Effect of DQS on tear fluid secretion in diabetic GK rats exposed to airflow for 8 weeks. GK rats underwent instillation with saline or DQS six times daily for 6 weeks. Each measurement was obtained before and after the instillation period. Each column represents mean ± SE (n = 12 eyes). **p < 0.01 vs GK/saline at the same time point (Student’s t-test). Abbreviations: DQS, 3% diquafosol tetrasodium ophthalmic solution; N.S., not significant; GK, Goto–Kakizaki, SE, standard error.
Figure 3
Figure 3
Effect of DQS on corneal fluorescein staining score in diabetic rats exposed to constant airflow. Male GK rats were maintained with constant airflow while subjected to instilled saline or DQS for 6 weeks. The corneal staining score was determined before instillation and at 2-, 4-, and 6-week instillations. (A) Representative images of the corneal epithelium with fluorescein staining in rats at 6-week instillation. Wistar rat served as control. (B) Time course of corneal fluorescein staining score. Each point represents the mean ± SE (n = 18 eyes). *p < 0.05, **p < 0.01 vs GK/saline (Student’s t-test). ##p < 0.01 vs Wistar (Student’s t-test). Abbreviations: DQS, 3% diquafosol tetrasodium ophthalmic solution; GK, Goto–Kakizaki, SE, standard error

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