scholarly journals Potential Therapeutic Role of Pituitary Adenylate Cyclase-Activating Polypeptide for Dry Eye Disease

2022 ◽  
Vol 23 (2) ◽  
pp. 664
Author(s):  
Takahiro Hirabayashi ◽  
Junko Shibato ◽  
Ai Kimura ◽  
Michio Yamashita ◽  
Fumiko Takenoya ◽  
...  
Keyword(s):  
Adenylate Cyclase ◽  
Dry Eye ◽  
Dry Eye Disease ◽  
Eye Disease ◽  
Tear Secretion ◽  
Corneal Injury ◽  
Pituitary Adenylate Cyclase ◽  
Aging Populations ◽  
Potential Therapeutic Role ◽  
Rapid Pace

Dry eye disease (DED) is caused by a reduction in the volume or quality of tears. The prevalence of DED is estimated to be 100 million in the developed world. As aging is a risk factor for DED, the prevalence of DED is expected to grow at a rapid pace in aging populations, thus creating an increased need for new therapies. This review summarizes DED medications currently in clinical use. Most current medications for DED focus on stimulating tear secretion, mucin secretion, or suppressing inflammation, rather than simply replenishing the ocular surface with moisture to improve symptoms. We recently reported that the neuropeptide PACAP (pituitary adenylate cyclase-activating polypeptide) induces tear secretion and suppresses corneal injury caused by a reduction in tears. Moreover, it has been reported that a PACAP in water and a 0.9% saline solution at +4 °C showed high stability and achieved 80–90% effectiveness after 2 weeks of treatment. These results reveal PACAP as a candidate DED medication. Further research on the clinical applications of PACAP in DED is necessary.

Emerging targets of inflammation and tear secretion in dry eye disease

2019 ◽  
Vol 24 (8) ◽  
pp. 1427-1432 ◽  
Author(s):  
Maria Markoulli ◽  
Alex Hui
Keyword(s):  
Dry Eye ◽  
Dry Eye Disease ◽  
Eye Disease ◽  
Tear Secretion

scholarly journals Association between aging-dependent gut microbiome dysbiosis and dry eye severity in C57BL/6 male mouse model: a pilot study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chang Ho Yoon ◽  
Jin Suk Ryu ◽  
Jayoon Moon ◽  
Mee Kum Kim
Keyword(s):  
Pilot Study ◽  
Dry Eye ◽  
Gut Microbiome ◽  
Dry Eye Disease ◽  
Eye Disease ◽  
Male Mice ◽  
Tear Secretion ◽  
Gut Dysbiosis ◽  
Α Diversity ◽  
Corneal Staining

Abstract Background While aging is a potent risk factor of dry eye disease, age-related gut dysbiosis is associated with inflammation and chronic geriatric diseases. Emerging evidence have demonstrated that gut dysbiosis contributes to the pathophysiology or exacerbation of ocular diseases including dry eye disease. However, the relationship between aging-related changes in gut microbiota and dry eye disease has not been elucidated. In this pilot study, we investigated the association between aging-dependent microbiome changes and dry eye severity in C57BL/6 male mice. Results Eight-week-old (8 W, n = 15), one-year-old (1Y, n = 10), and two-year-old (2Y, n = 8) C57BL/6 male mice were used. Dry eye severity was assessed by corneal staining scores and tear secretion. Bacterial genomic 16 s rRNA from feces was analyzed. Main outcomes were microbiome compositional differences among the groups and their correlation to dry eye severity. In aged mice (1Y and 2Y), corneal staining increased and tear secretion decreased with statistical significance. Gut microbiome α-diversity was not different among the groups. However, β-diversity was significantly different among the groups. In univariate analysis, phylum Firmicutes, Proteobacteria, and Cyanobacteria, Firmicutes/Bacteroidetes ratio, and genus Alistipes, Bacteroides, Prevotella, Paraprevotella, and Helicobacter were significantly related to dry eye severity. After adjustment of age, multivariate analysis revealed phylum Proteobacteria, Firmicutes/Bacteroidetes ratio, and genus Lactobacillus, Alistipes, Prevotella, Paraprevotella, and Helicobacter to be significantly associated with dry eye severity. Conclusions Our pilot study suggests that aging-dependent changes in microbiome composition are related to severity of dry eye signs in C57BL/6 male mice.

scholarly journals Aged Mice Devoid of the M3 Muscarinic Acetylcholine Receptor Develop Mild Dry Eye Disease

2021 ◽  
Vol 22 (11) ◽  
pp. 6133
Author(s):  
Aytan Musayeva ◽  
Subao Jiang ◽  
Yue Ruan ◽  
Jenia Kouchek Zadeh ◽  
Panagiotis Chronopoulos ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Dry Eye ◽  
Ocular Surface ◽  
Dry Eye Disease ◽  
Eye Disease ◽  
Receptor Subtype ◽  
Redox Enzymes ◽  
Tear Secretion ◽  
Tear Production ◽  
M3 Receptor

The parasympathetic nervous system is critically involved in the regulation of tear secretion by activating muscarinic acetylcholine receptors. Hence, various animal models targeting parasympathetic signaling have been developed to induce dry eye disease (DED). However, the muscarinic receptor subtype (M1–M5) mediating tear secretion remains to be determined. This study was conducted to test the hypothesis that the M3 receptor subtype regulates tear secretion and to evaluate the ocular surface phenotype of mice with targeted disruption of the M3 receptor (M3R−/−). The experimental techniques included quantification of tear production, fluorescein staining of the ocular surface, environmental scanning electron microscopy, assessment of proliferating cells in the corneal epithelium and of goblet cells in the conjunctiva, quantification of mRNA for inflammatory cytokines and prooxidant redox enzymes and quantification of reactive oxygen species. Tear volume was reduced in M3R−/− mice compared to age-matched controls at the age of 3 months and 15 months, respectively. This was associated with mild corneal epitheliopathy in the 15-month-old but not in the 3-month-old M3R−/− mice. M3R−/− mice at the age of 15 months also displayed changes in corneal epithelial cell texture, reduced conjunctival goblet cell density, oxidative stress and elevated mRNA expression levels for inflammatory cytokines and prooxidant redox enzymes. The findings suggest that the M3 receptor plays a pivotal role in tear production and its absence leads to ocular surface changes typical for DED at advanced age.

scholarly journals Small‐molecule CFTR activators increase tear secretion and prevent experimental dry eye disease

2016 ◽  
Vol 30 (5) ◽  
pp. 1789-1797 ◽  
Author(s):  
Alyssa M. Mores ◽  
Scott D. Casey ◽  
Christian M. Felix ◽  
Puay W. Phuan ◽  
A. S. Verkman ◽  
...  
Keyword(s):  
Small Molecule ◽  
Dry Eye ◽  
Dry Eye Disease ◽  
Eye Disease ◽  
Tear Secretion

scholarly journals Randomized, crossover clinical efficacy trial in humans and mice on tear secretion promotion and lacrimal gland protection by molecular hydrogen

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Miyuki Kubota ◽  
Motoko Kawashima ◽  
Sachiko Inoue ◽  
Toshihiro Imada ◽  
Shigeru Nakamura ◽  
...  
Keyword(s):  
Dry Eye ◽  
Molecular Hydrogen ◽  
Human Subjects ◽  
Dry Eye Disease ◽  
Eye Disease ◽  
Efficacy Trial ◽  
Tear Secretion ◽  
Eye Symptoms ◽  
New Treatment ◽  
Dry Eye Symptoms

AbstractThe incidence of dry eye disease is increasing worldwide because of the aging population and increasing use of information technology. Dry eye disease manifests as tear-layer instability and inflammation caused by osmotic hypersensitization in tear fluids; however, to our knowledge, no agent that treats both pathologies simultaneously is available. Molecular hydrogen (H2) is known to be effective against various diseases; therefore, we aimed to elucidate the effects of H2on tear dynamics and the treatment of dry eye disease. We revealed that administering a persistent H2-generating supplement increased the human exhaled H2concentration (p < 0.01) and improved tear stability (p < 0.01) and dry eye symptoms (p < 0.05) significantly. Furthermore, H2significantly increased tear secretion in healthy mice (p < 0.05) and significantly suppressed tear reduction in a murine dry eye model (p = 0.007). H2significantly and safely improved tear stability and dry eye symptoms in a small exploratory group of 10 human subjects, a subset of whom reported dry eye symptoms prior to treatment. Furthermore, it increased tear secretion rapidly in normal mice. Therefore, H2may be a safe and effective new treatment for dry eye disease and thus larger trials are warranted.

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