Anti-inflammation effects of Zidovudine in human corneal epithelial cells

Abstract

Purpose : Dry eye disease (DED) is a common ocular surface inflammatory disease, which can significantly impact the quality of life of patients. Activation of NLRP3 inflammasome and downstream casepase-1 and IL-1β activation and maturation play critical roles in the pathophysiology of DED. The purpose of this study is to determine the effect of Zidovudine (AZT), a nucleoside reverse transcriptase inhibitor, on inflammasome activation in corneal epithelial cells, a hyperosmolarity dry eye model.

Methods : Immortalized human corneal epithelial cells (HCECs) were pretreated in the presence or absence of 100mM and 200mM of AZT for 2 hours. HCECs were then exposed to media ranging from 312 mOsm (normal osmolarity) to 500 mOsm (hyperosmolarity). Cell culture supernatants were collected at 4, 12, and 24 hours. Epithelial cell viability and level of IL-1β were determined by a lactate dehydrogenase (LDH) assay and a specific capture ELISA (eBioscience).

Results : In the hyperosmolarity group, the LDH ratio and level of IL-1β were significantly increased as compared to the normal control osmolarity group. In the hyperosmolarity group pretreated with 100mM and 200mM AZT, the LDH ratio and IL-1β level were decreased as compared to non-AZT-treated hyperosmolarity group.

Conclusions : AZT can improve HCECs survival as evidenced by decreased LDH ratio and inhibit the production of the inflammatory cytokines IL-1β. Nucleoside reverse transcriptase inhibitors like AZT may be useful for the management of DED.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.