Mitochondrial Dysfunction as a Contributing Cause of Dry Eye Disease
One of the components of declining mitochondrial function throughout the body with advancing age is a reduction in mitochondrial quality control, the complex process of mitophagy responsible for recycling damaged mitochondria. Increased mitophagy has been shown to improve mitochondrial function in a number of contexts. Researchers here note the contribution of mitochondrial dysfunction to the aging of the lacrimal gland, contributing to dry eye syndrome - an underappreciated and highly unpleasant feature of aging. Improved mitophagy leads to improved lacrimal gland function, a potential basis for novel therapies.
Dry eye disease (DED) is one of the most common ocular surface diseases affecting the quality of life of the elderly population, and aging is also one of the independent risk factors for DED. The lacrimal gland is an exocrine gland that contributes mainly to the aqueous component of the tear film, and its secretion constitutes the majority of the tear film (98% to 99%). It consists of three main cell types: acinar epithelial cells, ductal epithelial cells, and myoepithelial cells. The most abundant type (about 80%), the acinar epithelial cells are highly polarized epithelial cells responsible for the synthesis and secretion of aqueous fluid.
The lacrimal gland is highly susceptible to the effects of aging, which manifests as structural and functional damage, with major pathological changes, including acinar epithelial cells atrophy, periductal fibrosis, and chronic inflammatory cells infiltration, as well as a decrease in the density of nerves driving lacrimal secretion, which ultimately leads to qualitative and quantitative abnormalities in lacrimal gland secretions.
In this study, we discovered that aging increased oxidative stress, which increased apoptosis, and generated reactive oxygen species (ROS) in acinar epithelial cells. Furthermore, activation of PINK1/Parkin-mediated mitophagy by rapamycin reduced lacrimal gland ROS concentrations and prevented aging-induced apoptosis of acinar cells, thereby causing histological alterations, microstructural degradation, and increasing tear secretion associated with ROS accumulation. Overall, our findings suggested that aging could impair mitochondrial function of acinar cells, and age-related alterations may be treated with therapeutic approaches that enhance mitophagy while maintaining mitochondrial function.