In Vitro Study finds NMN and melatonin enhance cell survival and tear protein production — Evidence Review
Published in Stem Cell Reports, by researchers from University of Birmingham
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Table of Contents
A new study from the University of Birmingham shows that impaired autophagy in human tear gland organoids disrupts cell survival and tear protein production, and that NMN or melatonin can partially restore these deficits. These findings align with existing research highlighting cellular dysfunction and inflammation as central to dry eye disease.
- The study's focus on autophagy and tear gland health complements prior research identifying inflammation and immune dysregulation as core mechanisms of dry eye, suggesting that impaired cellular maintenance may contribute to the inflammatory cycle 1 2 4 5.
- While most previous studies center on inflammation and immune responses, a few have begun to explore regenerative and cell-based therapies, including stem cell-derived treatments, which are consistent with the new study's use of organoids and its emphasis on cellular restoration [6-10].
- The demonstration that NMN and melatonin can improve cell survival and tear protein output provides a novel mechanistic link between cellular metabolism, gland health, and potential therapeutic strategies, expanding on earlier evidence that regenerative approaches may benefit ocular surface diseases 6 8 9.
Study Overview and Key Findings
Dry eye disease (DED) is a widespread, multifactorial condition that can severely impact visual comfort and quality of life. While inflammation has long been recognized as a key driver of DED, the precise cellular processes underlying gland dysfunction remain incompletely understood. This study addresses a critical gap by investigating the role of autophagy—a cellular cleanup and recycling process—in the maintenance and function of human tear glands.
By generating human tear gland organoids from stem cells, researchers were able to model both healthy and impaired glandular conditions in vitro. This approach allowed for direct manipulation of autophagy pathways, providing insight into how disruptions at the cellular level can lead to DED-like symptoms and suggesting possible intervention points.
| Property | Value |
|---|---|
| Organization | University of Birmingham |
| Journal Name | Stem Cell Reports |
| Authors | Sovan Sarkar |
| Population | Human tear glands |
| Methods | In Vitro Study |
| Outcome | Tear protein production, cell survival |
| Results | NMN or melatonin improved cell survival and tear protein production. |
Literature Review: Related Studies
To understand how these findings fit into the broader research landscape, we conducted a search of the Consensus paper database, which includes over 200 million research papers. The following queries were used to identify relevant studies:
- dry eye disease cellular mechanisms
- NMN melatonin tear protein production
- cell survival treatments dry eye disease
Below, key topics from the related literature are summarized:
| Topic | Key Findings |
|---|---|
| What are the core cellular and molecular mechanisms in dry eye disease? | - Chronic inflammation, immune dysregulation, and epithelial cell dysfunction are central mechanisms in dry eye pathogenesis 1 2 4 5. - Cytotoxic inflammatory mediators, altered tear gland secretion, and impaired nerve function perpetuate tissue damage and symptoms 2 5. |
| How do regenerative and cell-based therapies contribute to treating DED? | - Stem cell-derived therapies, including mesenchymal stem cells and their exosomes, can reduce inflammation, promote tissue repair, and improve tear production in experimental models [6-10]. - Cell-free therapies, such as extracellular vesicles and targeted microRNAs, show promise for restoring ocular surface health 7 8. |
| What is the evidence for targeting cellular processes such as autophagy, metabolism, or cell survival in DED? | - Novel treatments targeting cellular health (e.g., nerve growth factor, metabolic support) are emerging, though direct studies on autophagy and metabolic interventions like NMN and melatonin in DED are limited 5 6 8. - Enhancement of cell survival and repair mechanisms is associated with improved outcomes in preclinical models 8 10. |
| How does inflammation interact with cellular dysfunction in DED progression? | - Inflammatory cascades are initiated and sustained by epithelial cell stress and damage, often resulting from tear film instability or environmental triggers 1 2 4. - Epithelial and immune cells engage in a feedback loop of inflammation and cell death, which amplifies disease severity 3 4. |
What are the core cellular and molecular mechanisms in dry eye disease?
Current research consistently identifies DED as a multifactorial disease rooted in chronic inflammation, epithelial dysfunction, and immune dysregulation. The new organoid study complements this view by demonstrating that impaired autophagy—a cellular housekeeping process—can directly disrupt tear gland homeostasis, suggesting that cellular maintenance pathways are integral to the disease process.
- Chronic inflammation is central, with both innate and adaptive immune responses implicated in tissue damage and symptom exacerbation 1 2 4.
- Epithelial cell stress, tear hyperosmolarity, and immune cell activation form a vicious cycle that perpetuates ocular surface disease 2 4 5.
- Disruption of normal cellular processes, such as autophagy, may underlie gland dysfunction in DED, expanding the traditional focus beyond inflammation alone 1 5.
- The new study’s findings on autophagy link cellular housekeeping failure to established mechanisms of epithelial damage and inflammation 1 2 5.
How do regenerative and cell-based therapies contribute to treating DED?
Recent advances highlight the promise of regenerative strategies, particularly those involving stem cells and cell-derived products, in restoring tissue function and reducing inflammation in DED. The use of lab-grown tear gland organoids in the new study is aligned with this growing interest in biologically based therapies.
- Mesenchymal stem cells (MSCs) and their exosomes have demonstrated anti-inflammatory and tissue-repair properties in preclinical and early clinical investigations 6 8 9 10.
- Cell-free therapies, including extracellular vesicles and microRNAs, can modulate inflammation and promote corneal healing without the risks associated with live cell transplantation 7 8 9.
- Regenerative medicine approaches are increasingly viewed as adjuncts or alternatives to traditional anti-inflammatory and lubricating treatments 6 9.
- The organoid platform offers a new tool for testing regenerative therapies and understanding cellular mechanisms in human-like systems 6 7.
What is the evidence for targeting cellular processes such as autophagy, metabolism, or cell survival in DED?
While anti-inflammatory agents remain the mainstay of therapy, there is growing attention to interventions that support cell survival, metabolic health, and tissue regeneration. The current organoid study is among the first to directly test metabolic and cellular support strategies (NMN and melatonin) in a controlled tear gland model.
- Novel therapeutic targets include nerve growth factor, metabolic modulators, and factors promoting cell survival and proliferation 5 6 8.
- Enhancing endogenous repair pathways and cellular homeostasis may complement inflammation control and improve long-term outcomes 5 8.
- Direct evidence for autophagy-based or metabolic interventions in DED is limited but expanding, with the new study providing experimental support for this approach 5 8.
- Cellular restoration strategies, including genetic and pharmacologic interventions, show promise in preclinical models but require further validation in human studies 8 10.
How does inflammation interact with cellular dysfunction in DED progression?
DED progression is now understood as a dynamic interplay between inflammation and cellular stress or dysfunction. The current study’s findings suggest that defects in autophagy may initiate or aggravate the inflammatory cycle by impairing gland function and increasing cell death.
- Epithelial cells are both targets and drivers of inflammation, responding to environmental and metabolic stress by releasing cytokines and danger signals 1 2 4.
- Inflammatory mediators amplify tissue damage, leading to further epithelial dysfunction and loss of tear film stability 2 4.
- Pyroptosis and other forms of inflammatory cell death are implicated in the progression of ocular surface damage 3.
- The new study’s focus on autophagy adds a new dimension to the understanding of how cellular defects may precede or exacerbate immune activation in DED 1 3 4.
Future Research Questions
Despite recent advances, key questions remain about the mechanisms and optimal management of dry eye disease. Further research is needed to clarify the role of autophagy in human tear glands, validate metabolic interventions, and translate organoid-based findings to clinical practice.
| Research Question | Relevance |
|---|---|
| How does autophagy in tear glands directly regulate inflammation and dry eye disease progression? | Understanding the interplay between autophagy and inflammation could clarify disease mechanisms and identify new therapeutic targets, as both processes are central to DED pathogenesis 1 2 5. |
| Can NMN or melatonin-based therapies improve clinical outcomes in patients with dry eye disease? | Preclinical evidence suggests these compounds may enhance cell survival and tear protein production, but their efficacy and safety in humans remain untested 6 8. |
| What are the long-term effects and safety of stem cell-derived organoid therapies for dry eye disease? | While organoid and cell-based therapies offer promise, rigorous studies are needed to assess their durability, integration, and risk profile in clinical settings 6 9. |
| How do cellular restoration strategies compare with traditional anti-inflammatory treatments in DED? | Direct comparisons are needed to determine whether targeting cellular homeostasis provides additional or synergistic benefits over current standard therapies, which mainly focus on inflammation control 1 5 6. |
| What biomarkers can predict response to regenerative or metabolic treatments in dry eye disease? | The identification of reliable biomarkers would enable personalized treatment strategies and facilitate clinical trials of new interventions targeting autophagy and cellular health 1 6. |