Dry Eye's Hidden Cause: Your Cellular Cleanup System

You have probably blamed your dry eyes on your screen, your office air conditioning, or just getting older. Those things can all play a role. But a study published in December 2025 in Stem Cell Reports suggests the real driver of dry eye disease may be happening much deeper, inside the tiny glands behind your eyelids that actually make your tears.

The researchers discovered that when a cellular process called autophagy fails inside these glands, the glands cannot produce healthy tears. And they found something remarkable: a molecule called NMN, a precursor to NAD+, was able to rescue the failing cells in the lab.

If you have chronic dry eyes and have never found a solution that fully works, this research offers something most dry eye coverage does not: a biological explanation that goes to the root of the problem.

Why Dry Eye Disease Is So Hard to Treat

Dry eye is one of the most common eye conditions in the United States, affecting tens of millions of people. Estimates of how many people have it range from 16 million to more than 30 million, depending on how it is defined and measured. The symptoms are wide-ranging: burning, stinging, grittiness, blurred vision, and a persistent feeling that something is stuck in your eye.

Most treatments focus on managing symptoms. Artificial tears replace moisture temporarily. Anti-inflammatory drops reduce irritation on the eye surface. Warm compresses help unclog the oil glands that keep tears from evaporating too quickly.

These approaches help a lot of people. But for many others, relief is incomplete or short-lived. That gap has pushed researchers to ask a more fundamental question: what is actually going wrong inside the glands that make tears?

Meet Your Tear Glands

Behind your upper eyelids sit your lacrimal glands. They are small, almond-shaped exocrine glands, meaning they produce and secrete substances outward, in this case onto the surface of your eye. These glands are responsible for the watery layer of your tear film, the thin coating that keeps your eye surface lubricated, protected, and clear.

When lacrimal glands malfunction, the tear film breaks down. The result is dry eye disease.

Most dry eye research has focused on what happens at the surface of the eye once the tears are gone. The University of Birmingham study asked a different question: what goes wrong inside the lacrimal glands themselves?

What Is Autophagy, and Why Does It Matter?

Autophagy is your cells' built-in cleanup system. The word comes from the Greek for "self-eating," which sounds alarming but describes something your body cannot function without. Autophagy is the process by which cells identify damaged proteins, worn-out organelles, and cellular debris, then break them down and recycle the components.

Think of it as a recycling program that runs continuously inside every cell in your body. When it works properly, cells stay clean, efficient, and functional. When it breaks down, damaged material accumulates and cell function deteriorates. The scientist who discovered how autophagy works, Yoshinori Ohsumi, was awarded the Nobel Prize in Physiology or Medicine in 2016, which tells you how fundamental this process is.

The University of Birmingham researchers wanted to know whether autophagy plays a role in lacrimal gland function. To find out, they used a technology called organoids: miniature, lab-grown tissue models made from stem cells that mimic the behavior of real organs. In this case, they grew tiny human tear glands from scratch.

What the Study Found

The team used human embryonic stem cells with autophagy deliberately switched off and guided them to develop into lacrimal gland-like organoids. The results were striking.

Without autophagy, the gland organoids showed improper development and impaired secretion. Damaged proteins accumulated inside the cells instead of being cleared out. Cell proliferation increased, and so did cell death.

Specifically, the researchers identified a transcription factor called PAX6, which plays a critical role in eye and brain development, building up inside the cells when autophagy was absent. PAX6 is normally cleared out by autophagy once it has done its job. When autophagy fails, PAX6 accumulates and disrupts normal cell behavior.

Here is where the finding becomes particularly interesting.

The team tested whether they could rescue the failing organoids with pharmacological interventions. Two compounds worked: melatonin and NMN, which stands for nicotinamide mononucleotide. NMN is a precursor to NAD+, the coenzyme your cells use to generate energy. When the researchers introduced NMN, cellular function in the autophagy-deficient organoids improved.

This was a lab study using organoids, not a clinical trial in human patients with dry eye disease. That distinction matters, and it is worth saying clearly: the study shows a mechanism and a potential intervention in a highly controlled lab setting. It does not prove that NMN supplementation treats dry eye in people. But the mechanism it points to, autophagy failure leading to lacrimal gland dysfunction, is a biologically plausible explanation for why so many dry eye patients do not fully respond to surface treatments.

The NMN and NR Connection

NMN is not the only route to raising NAD+ levels in cells. NR, or nicotinamide riboside, is another NAD+ precursor that operates through the same core pathway.

Based on articles retrieved from PubMed, a review published in Aging Medicine examined the key NAD+ precursors, including NR and NMN, and found that both effectively raise NAD+ levels in human cells. The pathway runs like this: when NR enters a cell, it is converted to NMN, which is then used to synthesize NAD+. NR and NMN are not competing alternatives; they are two steps in the same chain.

Sight Guard was formulated with Nicotinamide Riboside (NR) at 300 mg because of its role in supporting NAD+ production and cellular energy in the eye. The study's finding that NMN supports lacrimal gland function through the NAD+ pathway is consistent with the broader science on how NAD+ precursors support cellular health across tissues, including the eye.

To be clear: this is not a claim that Sight Guard treats or prevents dry eye disease. The University of Birmingham study was conducted in organoids, and the therapeutic implications for human patients remain to be studied. What the science does suggest is that NAD+ production and cellular energy are relevant to lacrimal gland function, and that this is an area of active, serious investigation.

What Does This Mean for You?

If you have dry eye disease, continue working with your eye care provider. Surface treatments, anti-inflammatory drops, and warm compresses remain the standard of care, and for good reason. None of what this study found changes that.

What it adds is a new window into why dry eye happens in the first place. If autophagy failure inside lacrimal glands is a real driver of the disease, it opens the door to treatments that work at the root cause rather than the symptoms. That is a meaningful shift in how researchers are thinking about the condition.

Supporting cellular energy through the NAD+ pathway is something many people already do as part of a proactive approach to vision wellness. For those interested in that kind of support, Sight Guard was formulated around the science of NAD+ and cellular energy in the eye, designed to complement, not replace, your existing care.

If dry eye is something you deal with regularly, it is worth bringing up with your eye doctor. Ask not just about surface treatments, but about the full picture of what may be driving it. The answer might surprise you.

The Bigger Picture

The University of Birmingham study is part of a broader shift in how researchers think about eye health. For decades, the dominant approach to dry eye was to replace what was missing at the surface. The new question is different: what is breaking down inside the cells that produce tears, and can that be fixed?

Autophagy sits at the center of some of the most active science in aging biology. The fact that lacrimal gland function depends on this cellular cleanup process suggests that dry eye disease may be, at least in part, a disease of cellular aging. That reframing matters because it points toward interventions that work with the biology of the cell, not just the surface of the eye.

That story is still being written. But the direction it is pointing is worth paying attention to.

References

1. Kocak G et al., "Autophagy is required for the development and functionality of lacrimal gland-like organoids." Stem Cell Reports, 2025, Vol. 21, Issue 1, p. 102744. PMID: 41418785. DOI: 10.1016/j.stemcr.2025.102744

2. Palmer RD et al., "Precursor comparisons for the upregulation of nicotinamide adenine dinucleotide. Novel approaches for better aging." Aging Medicine, 2021, Vol. 4, Issue 3, pp. 214-220. PMID: 34553119. DOI: 10.1002/agm2.12170

3. ScienceDaily. "A hidden cellular breakdown may be driving dry eye disease." December 25, 2025. Link

4. MedicalXpress. "Insights into dry eyes gained from stem-cell-derived tear glands." December 2025. Link

5. ISSCR. "Insights Into Dry Eyes Gained from Stem cell-derived Tear Glands." 2025. Link