HMN 2025: What are the Insights into dry eyes gained from stem-cell-derived tear glands

An estimated 5–15% of people have problems with dry eyes, with symptoms including eye redness, stinging, or burning sensation, and eye fatigue.

Dry eye disease (DED) occurs when the eyes’ tear glands produce insufficient or poor-quality tears, which can be due to allergy or autoimmune disease, hormonal changes, aging, etc. When left untreated, DED can increase the risk of eye infections and abrasion damage to the ocular surface, which may impair vision.

Exploring autophagy in tear glands

A process called autophagy, which is needed to clear up a cell’s interior from damaged proteins etc., is thought to be compromised in tear glands of people with DED. To understand the connection between DED and autophagy and to potentially open up new therapeutic avenues, Sovan Sarkar and his team from the University of Birmingham, UK, have generated tear gland organoids from stem cells, 3D structures resembling human tear glands.

The work is published in Stem Cell Reports.

Findings from organoid research

The organoids contained the different cell types which build up human tear glands and made tear proteins required for eye lubrication and for the prevention of infections. Interestingly, when autophagy was disabled in the organoids using a genetic tool, the cellular composition of the organoids was disrupted, the secretion of tear proteins was reduced, and cell death was increased.

Pharmacological intervention with nicotinamide mononucleotide (NMN) or melatonin had a beneficial effect in this model and helped to prevent cell death and to restore tear protein secretion in the autophagy-deficient organoids.

“Autophagy is essential for proper tissue development and organ function. Here, we provide genetic evidence that autophagy is required for glandular tissue development by using autophagy-deficient human embryonic stem cells to generate tear glands with developmental and functional defects,” Sarkar said.

This new human stem cell-based tear gland model will be an accessible tool to study tear gland function and how it can be modulated to prevent or treat DED.

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