ReviewJournal of molecular neuroscience : MN2022
Is the Sex Difference a Clue to the Pathomechanism of Dry Eye Disease? Watch out for the NGF-TrkA-Piezo2 Signaling Axis and the Piezo2 Channelopathy.
Review in Journal of molecular neuroscience : MN, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 32 citations in OpenAlex.
- The Impact of Aging and Sex on Corneal Nerve Density and Function.Investigative ophthalmology & visual science · 2026Article
- Electrotherapy in the management of neuropathic corneal pain: narrative review.Experimental biology and medicine (Maywood, N.J.) · 2026Review
- It Is Time to Consider the Lost Battle of Microdamaged Piezo2 in the Context ofInternational journal of molecular sciences · 2025Review
- Delayed-Onset Muscle Soreness Begins with a Transient Neural Switch.International journal of molecular sciences · 2025Review
- Piezo in the eye: expression, distribution and roles in ocular diseases.Frontiers in physiology · 2025Review
- Proton-Mediated PIEZO2 Channelopathy: Linking Oxaliplatin Treatment to Impaired Proprioception and Cognitive Deficits.Cancers · 2024Article
- Prohibited Olympic Medalist with PIEZO1 VUS Who Claims Innocence.International journal of molecular sciences · 2024Article
- Article
- The Role of Mechanosensitive Piezo Channels in Chronic Pain.Journal of pain research · 2024Review
- Orthostasis Is Impaired Due to Fatiguing Intensive Acute Concentric Exercise Succeeded by Isometric Weight-Loaded Wall-Sit in Delayed-Onset Muscle Soreness: A Pilot Study.Sports (Basel, Switzerland) · 2023Article
- Disrupted Neural Regeneration in Dry Eye Secondary to Ankylosing Spondylitis-With a Theoretical Link between Piezo2 Channelopathy and Gateway Reflex, WDR Neurons, and Flare-Ups.International journal of molecular sciences · 2023Article
- Neural Regeneration in Dry Eye Secondary to Systemic Lupus Erythematosus Is Also Disrupted like in Rheumatoid Arthritis, but in a Progressive Fashion.International journal of molecular sciences · 2023Article
- Evidence of Disruption in Neural Regeneration in Dry Eye Secondary to Rheumatoid Arthritis.International journal of molecular sciences · 2023Article
- LF Power of HRV Could Be the Piezo2 Activity Level in Baroreceptors with Some Piezo1 Residual Activity Contribution.International journal of molecular sciences · 2023Article
- Miswired Proprioception in Amyotrophic Lateral Sclerosis in Relation to Pain Sensation (and in Delayed Onset Muscle Soreness)-Is Piezo2 Channelopathy a Principal Transcription Activator in Proprioceptive Terminals Besides Being the Potential Primary Damage?Life (Basel, Switzerland) · 2023Article
- Prevalence of Dry Eye Symptoms and Associated Risk Factors among University Students in Poland.International journal of environmental research and public health · 2023Article
- Psoriasis, Is It a Microdamage of Our "Sixth Sense"? A Neurocentric View.International journal of molecular sciences · 2022Article
- CD3International journal of molecular sciences · 2022Article
- Should We Void Lactate in the Pathophysiology of Delayed Onset Muscle Soreness? Not So Fast! Let's See a Neurocentric View!Metabolites · 2022Article
- Delayed Onset Muscle Soreness and Critical Neural Microdamage-Derived Neuroinflammation.Biomolecules · 2022Review
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dry eye disease (DED) is a multifactorial disorder with recognized pathology, but not entirely known pathomechanism. It is suggested to represent a continuum with neuropathic corneal pain with the paradox that DED is a pain-free disease in most cases, although it is regarded as a pain condition. The current paper puts into perspective that one gateway from physiology to pathophysiology could be a Piezo2 channelopathy, opening the pathway to a potentially quad-phasic non-contact injury mechanism on a multifactorial basis and with a heterogeneous clinical picture. The primary non-contact injury phase could be the pain-free microinjury of the Piezo2 ion channel at the corneal somatosensory nerve terminal. The secondary non-contact injury phase involves harsher corneal tissue damage with C-fiber contribution due to the lost or inadequate intimate cross-talk between somatosensory Piezo2 and peripheral Piezo1. The third injury phase of this non-contact injury is the neuronal sensitization process with underlying repeated re-injury of the Piezo2, leading to the proposed chronic channelopathy. Notably, sensitization may evolve in certain cases in the absence of the second injury phase. Finally, the quadric injury phase is the lingering low-grade neuroinflammation associated with aging, called inflammaging. This quadric phase could clinically initiate or augment DED, explaining why increasing age is a risk factor. We highlight the potential role of the NGF-TrkA axis as a signaling mechanism that could further promote the microinjury of the corneal Piezo2 in a stress-derived hyperexcited state. The NGF-TrkA-Piezo2 axis might explain why female sex represents a risk factor for DED.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.