Meibomian Gland and Ocular Surface Alterations in Sod1 Knock-Out Mice: A Novel Model for Age Related Dry Eye Disease

Abstract

Purpose: : The purpose of our study was to investigate the feasibility of (SOD1)-deficient (-/-) mice as a model of age related dry eye disease.

Methods: : Tear function tests [Break up time (BUT) and cotton thread] and corneal fluorescein staining tests were performed on SOD1- deficient (-/-) male mice (n=24) aged 10 and 50 weeks and age and sex matched wild-type (+/+) mice (n=20). Tear and serum samples were collected at sacrifice for inflammatory cytokine assays. Meibomian gland (MG) specimens underwent Hematoxylin and Eosin staining, Mallory staining for fibrosis. MG acinar unit density was assessed.The study was conducted in compliance with the Tennets of the Declaration of Helsinki and ARVO statement for the use of animals in Ophthalmic and Visual Research.

Results: : The mean BUT values in SOD1-deficient (-/-) mice were significantly lower compared with wild type mice throughout the follow up. Tear quantity values of the SOD1-deficient (-/-) mice were consistently lower compared to the wild-type (+/+) mice. Fluorescein staining scores were significantly higher in the SOD1-deficient (-/-) mice compared to the wild type mice. MG histopathology revealed a significant decrease in the density of acinar units, interacinar fibrosis and periacinar inflammatory infiltrates in the SOD-1 KO mice compared to the wild type. Tear and serum IL-6 and TNF-alpha also showed significant time wise elevations in the SOD1-deficient (-/-) mice.

Conclusions: : The SOD-1 knockout mouse has been reported to be a model mouse of aging, especially age related macular degeneration. Our preliminary results suggest that it may also serve as a mouse model of dry eye disease, which in part owes to MG alterations, and will provide invaluable information in the understanding of age related dry eye disease in humans.

Keywords: cornea: tears/tear film/dry eye • cytokines/chemokines • eyelid