Oxidative Stress Induced Age Dependent Meibomian Gland Dysfunction in Cu, Zn-Superoxide Dismutase-1 (Sod1) Knockout Mice

Abstract

PurposeThe purpose of our study was to investigate alterations in the meibomian gland (MG) in Cu, Zn-Superoxide Dismutase-1 knockout (Sod1 −/−) mouse.MethodsTear function tests [Break up time (BUT) and cotton thread] and ocular vital staining test were performed on Sod1 −/− male mice (n = 24) aged 10 and 50 weeks, and age and sex matched wild–type (+/+) mice (n = 25). Tear and serum samples were collected at sacrifice for inflammatory cytokine assays. MG specimens underwent Hematoxylin and Eosin staining, Mallory staining for fibrosis, Oil Red O lipid staining, TUNEL staining, immunohistochemistry stainings for 4HNE, 8-OHdG and CD45. Transmission electron microscopic examination (TEM) was also performed.ResultsCorneal vital staining scores in the Sod1 −/− mice were significantly higher compared with the wild type mice throughout the follow-up. Tear and serum IL-6 and TNF-α levels also showed significant elevations in the 10 to 50 week Sod1 −/− mice. Oil Red O staining showed an accumulation of large lipid droplets in the Sod1 −/− mice at 50 weeks. Immunohistochemistry revealed both increased TUNEL and oxidative stress marker stainings of the MG acinar epithelium in the Sod1 −/− mice compared to the wild type mice. Immunohistochemistry staining for CD45 showed increasing inflammatory cell infiltrates from 10 to 50 weeks in the Sod1 −/− mice compared to the wild type mice. TEM revealed prominent mitochondrial changes in 50 week Sod1 −/− mice.ConclusionsOur results suggest that reactive oxygen species might play a vital role in the pathogensis of meibomian gland dysfunction. The Sod1 −/− mouse appears to be a promising model for the study of reactive oxygen species associated MG alterations.

Dry eye disease and oxidative stress

“…) and increased meibomian gland dysfunction (MGD; Ibrahim et al. ). Meibomian gland (MGD), a problem associated with occlusion of the meibomian gland orifices, disrupts the delivery of critical meibum lipids to the tear film, and consequently disturbs tear stability and aggravates dry eye (Nichols et al.…”

Superoxide Dismutase Dysregulation Undermines Endogenous Antioxidant System and Promote Retinal Neurodegenerative Pathology

“…prolonged oxidative stress can also oxidise the methionine residues in various proteins such as serine protease inhibitors and inactivate them leading to uncontrolled proteolytic activation and this model will help to determine the role of tissue damage caused by uncontrolled proteolysis in the retin [12] . These animals exhibit increased levels of circulating interleukin-6 and increased TNFα levels [13] . Oxidative stress may contribute to mitochondrial swelling, disorientation, shortening, and disorganization of cristae 13 and mitochondrial aberrations are well known to play a role in several of the retinal degenerative diseases including glaucoma, age related macular degeneration (AMD) and other optic neuropathies [14] .…”

“…Oxidative stress may contribute to mitochondrial swelling, disorientation, shortening, and disorganization of cristae 13 and mitochondrial aberrations are well known to play a role in several of the retinal degenerative diseases including glaucoma, age related macular degeneration (AMD) and other optic neuropathies [14] . Interestingly eyelid inflammation and changes in body fluids like tear and serum have also been observed in superoxide dismutase knockout animals [13] . These animals depict accumulation of large lipid droplets in the acinar units of meibomian glands in old age.…”

“…These animals depict accumulation of large lipid droplets in the acinar units of meibomian glands in old age. Exposure to oxidative damage may also lead to ocular surface epithelial cell damage [13] . There is also a progressive loss of RGC density in the retina [15] .…”

Cell size and nucleo‐cytoplasmic ratios of meibocytes in the anterior acini of the upper eyelid Meibomian glands in rabbits

“…The actual secretory nature is not evident in such clumps with the units seen to have a relatively amorphous content such that the individual cells (meibocytes) are not uniformly evident. In other sections, perhaps at slightly higher magnification, some meibocyte nuclei can be visible, and just sometimes the individual meibocytes with their cell borders can be seen . The cells seen, however, do not have any obvious organization and so better sectioning and viewing methods as well as objective assessments are needed to underpin histopathological diagnoses of gland dysfunction.…”