Dry eye syndrome is a common condition that not only causes discomfort, but can affect the ocular surface and vision if left untreated. A new study suggests that the proper functioning of the tear glands depends on a fundamental cellular process responsible for removing damaged components from within the cells.
Between 5% and 15% of people worldwide experience dry eye symptoms such as redness, burning or stinging and eye fatigue.
Dry eye syndrome occurs when the lacrimal glands do not produce enough tears or when their quality is impaired. The condition can be associated with allergies, autoimmune diseases, hormonal changes, aging or other factors. Untreated, it can increase the risk of eye infections and can lead to damage to the surface of the eye, with impaired vision.
The researchers started from the hypothesis that in the lacrimal glands of people with dry eye syndrome, an essential cellular process called autophagy is disturbed. Autophagy represents an internal “cleaning” system of the cell, through which damaged proteins and other unnecessary components are removed, thus allowing the cells to function normally.
To investigate the role of this mechanism, a team from the University of Birmingham, in the UK, created tear gland organoids in the laboratory starting from stem cells.
These three-dimensional structures closely reproduce the characteristics of human lacrimal glands. The results were published in the journal Stem Cell Reports.
The obtained organoids contain all the types of cells normally found in the lacrimal glands and are able to produce tear proteins involved in the lubrication of the eye and protection against infections.
Immunofluorescence image of caspase-3 in its activated form in lacrimal gland-like organoids derived from autophagy-deficient human embryonic stem cells (hESCs), indicating high levels of cell death in the absence of autophagy. Credit: University of Birmingham
When researchers genetically disabled autophagy in these models, cellular balance was disrupted, tear protein production decreased, and the number of cells that died increased significantly.
In subsequent experiments, treatment of autophagy-deficient organoids with nicotinamide mononucleotide (NMN) or melatonin reduced the observed damage. Under these conditions, cell death was limited, and the release of tear proteins was partially restored in the experimental model.
According to the authors, the results provide genetic evidence that autophagy is necessary for the development and normal functioning of glandular tissue.
The human lacrimal gland model obtained from stem cells gives researchers an accessible tool to study how the lacrimal glands work and how their activity can be influenced.
In the future, this approach could support the development of new strategies to prevent or treat dry eye syndrome.