New lacrimal gland organelles shed light on dry eye biology

It is estimated that 5-15% of people have dry eye problems, with symptoms such as eye redness, stinging or burning, and eye fatigue. Dry eye disease (DED) occurs when the tear glands of the eyes produce insufficient or poor quality tears which may be due to allergy or autoimmune disease, hormonal changes, aging etc. When left untreated, DED can increase the risk of eye infections and frictional damage to the ocular surface, which can impair vision.

A process called autophagy, which is needed to clean the inside of a cell of damaged proteins, etc., is thought to be compromised in the tear glands of people with DED. To understand the link between DED and autophagy and potentially open new therapeutic avenues, Sovan Sarkar and his team from the University of Birmingham, UK, have created stem cell lacrimal organoids, three-dimensional structures that resemble human lacrimal glands. The project was recently published on Stem Cell Reports. These organoids contained the different types of cells that make up the human tear glands and made tear proteins needed to lubricate the eyes and prevent infection. Interestingly, when autophagy was disabled in the organelles using a genetic tool, cell synthesis of the organelles was disrupted, 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 prevent cell death and restore tear protein secretion in autophagy-deficient organoids.

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

Sovan Sarkar, University of Birmingham, UK

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