Toll-Like Receptors in InflammAging at Ocular Surface.

2021 ◽  
Author(s):  
Antonio Zazzo ◽  
Maria Piano ◽  
Alessandra Micera ◽  
Tommaso Mori ◽  
Marco Coassin
Keyword(s):  
Ocular Surface ◽  
Physiological Role ◽  
Goblet Cells ◽  
Epifluorescence Microscopy ◽  
Toll Like Receptors ◽  
Schirmer Test ◽  
Age Related ◽  
Healthy Control ◽  
Homeostatic Mechanisms

Abstract Purpose: To evaluate changes in Toll Like Receptors expression at the ocular surface of healthy control volunteers within age. Methods: 51 volunteers were enrolled in a pilot observational study. Clinical (OSDI questionnaire, Schirmer test and BUT) and Biomolecular (ICAM1, Goblet cells) biomarkers were assessed in all subjects. Temporal Conjunctival imprints were used for molecular analysis while nasal ones were harvested for epifluorescence microscopy. Results: Within the age in our sample OSDI score increases, T-BUT values decrease, and goblet cells showed a decreasing trend. Relative real time PCR detected up-regulation of TLR2 and down-regulation of TLR7, TLR8 and MyD88 transcripts. Immunofluorescence data corroborated the PCR results reporting increased TLR2 and decreased TLR7 and TLR8 expression in elder population. A direct correlation was showed between increasing ICAM and increasing TLR2 changes with age. Conclusion: Changes in TLR expression are associated with aging, suggesting physiological role of TLRs in modulating innate and adaptive ocular surface immunity. TLRs age related changes may participate to the failure of ocular surface homeostatic mechanisms with inflammAging.

scholarly journals Loss of Wwox Causes Defective Development of Cerebral Cortex with Hypomyelination in a Rat Model of Lethal Dwarfism with Epilepsy

2019 ◽  
Vol 20 (14) ◽  
pp. 3596 ◽  
Author(s):  
Yuki Tochigi ◽  
Yutaka Takamatsu ◽  
Jun Nakane ◽  
Rika Nakai ◽  
Kentaro Katayama ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Rat Model ◽  
Physiological Role ◽  
Early Death ◽  
Neurite Growth ◽  
Loss Of Function ◽  
Age Related ◽  
Putative Tumor Suppressor ◽  
Severe Reduction

WW domain-containing oxidoreductase (Wwox) is a putative tumor suppressor. Several germline mutations of Wwox have been associated with infant neurological disorders characterized by epilepsy, growth retardation, and early death. Less is known, however, about the pathological link between Wwox mutations and these disorders or the physiological role of Wwox in brain development. In this study, we examined age-related expression and histological localization of Wwox in forebrains as well as the effects of loss of function mutations in the Wwox gene in the immature cortex of a rat model of lethal dwarfism with epilepsy (lde/lde). Immunostaining revealed that Wwox is expressed in neurons, astrocytes, and oligodendrocytes. lde/lde cortices were characterized by a reduction in neurite growth without a reduced number of neurons, severe reduction in myelination with a reduced number of mature oligodendrocytes, and a reduction in cell populations of astrocytes and microglia. These results indicate that Wwox is essential for normal development of neurons and glial cells in the cerebral cortex.

scholarly journals Role of ion channels in the functional response of conjunctival goblet cells to dry eye

2018 ◽  
Vol 315 (2) ◽  
pp. C236-C246 ◽  
Author(s):  
Donald G. Puro
Keyword(s):  
Ion Channels ◽  
Dry Eye ◽  
Ocular Surface ◽  
Adaptive Response ◽  
Tear Film ◽  
Goblet Cells ◽  
Cation Conductance ◽  
Conjunctival Goblet Cells

Optimal vision requires an ocular surface with a stable tear film whose many critical tasks include providing >70% of the eye’s refractive power. However, for millions, tear film instability produces uncomfortable sight-impairing dry eye. Despite the multitude of etiologies for dry eye, a universal hallmark is hyperosmolarity of the tear film. Presently, knowledge of how the ocular surface responds to hyperosmolarity remains incomplete with little understood about the role of ion channels. This bioelectric analysis focused on conjunctival goblet cells whose release of tear-stabilizing mucin is a key adaptive response to dry eye. In freshly excised rat conjunctiva, perforated-patch recordings demonstrated that a ≥10% rise in osmolarity triggers goblet cells to rapidly generate a ~15-mV hyperpolarization due to the oxidant-dependent activation of ATP-sensitive K+ (KATP) channels. High-resolution membrane capacitance measurements used to monitor exocytosis revealed that this hyperpolarization results in an approximately fourfold boost in exocytotic activity evoked by cholinergic input, which in vivo occurs via a neural reflex and depends chiefly on calcium influxing down its electro-gradient. We discovered that this adaptive response is transient. During 30–80 min of hyperosmolarity, development of a depolarizing nonspecific cation conductance fully counterbalances the KATP-driven hyperpolarization and thereby eliminates the exocytotic boost. We conclude that hyperosmotic-induced hyperpolarization is a previously unappreciated mechanism by which goblet cells respond to transient ocular dryness. Loss of this voltage increase during long-term dryness/hyperosmolarity may account for the clinical conundrum that goblet cells in chronically dry eyes can remain filled with mucin even though the tear film is hyperosmotic and mucin-deficient.

scholarly journals What is the physiological role of hypothalamic tanycytes in metabolism?

2021 ◽  
Author(s):  
Matei Bolborea ◽  
Fanny Langlet
Keyword(s):  
Energy Balance ◽  
Metabolic Disorders ◽  
Neural Circuits ◽  
Physiological Function ◽  
Physiological Role ◽  
Optimal Conditions ◽  
Age Related ◽  
New Research ◽  
Opening Up

In vertebrates, the energy balance process is tightly controlled by complex neural circuits that sense metabolic signals and adjust food intake and energy expenditure in line with the physiological requirements of optimal conditions. Within neural networks controlling energy balance, tanycytes are peculiar ependymoglial cells that are nowadays recognized as multifunctional players in the metabolic hypothalamus. However, the physiological function of hypothalamic tanycytes remains unclear, creating a number of ambiguities in the field. Here, we review data accumulated over the years that demonstrate the physiological function of tanycytes in the maintenance of metabolic homeostasis, opening up new research avenues. The presumed involvement of tanycytes in the pathophysiology of metabolic disorders and age-related neurodegenerative diseases will be finally discussed.

scholarly journals Apolipoprotein D Concentration in Human Plasma during Aging and in Parkinson’s Disease: A Cross-Sectional Study

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Andreas Waldner ◽  
Sarah Dassati ◽  
Bernhard Redl ◽  
Nicola Smania ◽  
Marialuisa Gandolfi
Keyword(s):  
Healthy Subjects ◽  
Neurological Impairment ◽  
Cross Sectional Study ◽  
Cross Sectional ◽  
Age Related ◽  
Healthy Control ◽  
Apolipoprotein D ◽  
The Relationship ◽  
Small Hydrophobic

Apolipoprotein D (ApoD), a lipocalin transporter of small hydrophobic molecules, plays an important role in several neurodegenerative diseases. ApoD is expressed in and secreted from a variety of peripheral and brain tissues. Increments of ApoD have been reported in relation with oxidative stress conditions, aging, and degeneration in the nervous system. Preliminary findings support the role of ApoD in neuroprotection. However, its role in PD remains unclear. To date, no studies have been performed on the relationship between ApoD in the blood and PD, as neurodegenerative pathology related to oxidative damage. We investigated the concentration of ApoD in the blood of healthy control subjects and PD patients with mild-to-moderate neurological impairment. ApoD plasma levels were measured using sandwich enzyme-linked immunosorbent assays (ELISA) in 90 healthy subjects (aging-analysis cohort) and in 66 PD patients at different stages compared with 19 age-matched healthy subjects. Significant age-related increase of ApoD was detected in subjects older than 65 years of age (p<0.002). In PD patients, a significant increase in ApoD plasma concentration was found compared with healthy subjects of the same age (p<0.05). ApoD and PD stage are significantly correlated (p<0.05). ApoD might be a valid marker for the progression of PD.

scholarly journals Evaluation of the association between exosomal levels and female reproductive system and fertility outcome during aging: a systematic review protocol

2019 ◽  
Vol 8 (1) ◽  
Author(s):  
Halimeh Mobarak ◽  
Reza Rahbarghazi ◽  
Francesca Lolicato ◽  
Mohammad Heidarpour ◽  
Fariba Pashazadeh ◽  
...  
Keyword(s):  
Systematic Review ◽  
Reproductive System ◽  
Reproductive Tract ◽  
Physiological Role ◽  
Current Evidence ◽  
Gene Expressions ◽  
Younger Women ◽  
Age Related ◽  
Maternal Aging

Abstract Background Exosomes may have critical roles in the maternal-embryo cross-talk for the recognition and maintenance of pregnancy during maternal aging. Exosomes have the capability to carry developmental signaling molecules with the ability to modulate gene expressions and affect growth and regulation of embryo during pregnancy. Systematic review aims to evaluate age-related alterations in the exosomal content and functions that can influence the reproductive performance in human and animal models as conveyors of senescence signals. Methods A literature search of electronic databases including MEDLINE (PubMed), Embase, ProQuest, Scopus, Google Scholar, WHO, SID, MAGIRAN, and Barakat will be conducted. Following the online search, articles will be screened by two independent reviewers according to inclusion and exclusion criteria. Eligible studies will be critically appraised by reviewers at the study level for methodological quality using Joanna Briggs Institute’s standardized critical appraisal tools. The extracted data from selected studies will cover the study populations, methods, current evidence about the physiological role of extracellular vesicles and exosomes in reproductive system, relevant outcomes, and possible conclusions about the effectiveness of exposure. Discussion Regarding the role of exosomes and their cargoes in the function of reproductive tract, the possible beneficial or adverse effects following exosomal administration from younger women to older women will be evaluated in the systematic review. As a result, exosome therapy could be suggested as a novel therapeutic agent if the favorable results are identified.

scholarly journals Activation of KCNQ4 as a Therapeutic Strategy to Treat Hearing Loss

2021 ◽  
Vol 22 (5) ◽  
pp. 2510
Author(s):  
John Hoon Rim ◽  
Jae Young Choi ◽  
Jinsei Jung ◽  
Heon Yung Gee
Keyword(s):  
Hearing Loss ◽  
Late Onset ◽  
Ion Homeostasis ◽  
Physiological Role ◽  
Voltage Gated ◽  
Age Related ◽  
Gated Channel ◽  
Pros And Cons ◽  
Age Related Hearing Loss

Potassium voltage-gated channel subfamily q member 4 (KCNQ4) is a voltage-gated potassium channel that plays essential roles in maintaining ion homeostasis and regulating hair cell membrane potential. Reduction of the activity of the KCNQ4 channel owing to genetic mutations is responsible for nonsyndromic hearing loss, a typically late-onset, initially high-frequency loss progressing over time. In addition, variants of KCNQ4 have also been associated with noise-induced hearing loss and age-related hearing loss. Therefore, the discovery of small compounds activating or potentiating KCNQ4 is an important strategy for the curative treatment of hearing loss. In this review, we updated the current concept of the physiological role of KCNQ4 in the inner ear and the pathologic mechanism underlying the role of KCNQ4 variants with regard to hearing loss. Finally, we focused on currently developed KCNQ4 activators and their pros and cons, paving the way for the future development of specific KCNQ4 activators as a remedy for hearing loss.

scholarly journals Synuclein Deficiency Results in Age-Related Respiratory and Cardiovascular Dysfunctions in Mice

2020 ◽  
Vol 10 (9) ◽  
pp. 583
Author(s):  
Patrick S. Hosford ◽  
Natalia Ninkina ◽  
Vladimir L. Buchman ◽  
Jeffrey C. Smith ◽  
Nephtali Marina ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Physiological Role ◽  
Normal Function ◽  
Whole Body ◽  
Cardiovascular Reflexes ◽  
Long Term Effects ◽  
Gene Encoding ◽  
Age Related

Synuclein (α, β, and γ) proteins are highly expressed in presynaptic terminals, and significant data exist supporting their role in regulating neurotransmitter release. Targeting the gene encoding α-synuclein is the basis of many animal models of Parkinson’s disease (PD). However, the physiological role of this family of proteins in not well understood and could be especially relevant as interfering with accumulation of α-synuclein level has therapeutic potential in limiting PD progression. The long-term effects of their removal are unknown and given the complex pathophysiology of PD, could exacerbate other clinical features of the disease, for example dysautonomia. In the present study, we sought to characterize the autonomic phenotypes of mice lacking all synucleins (α, β, and γ; αβγ−/−) in order to better understand the role of synuclein-family proteins in autonomic function. We probed respiratory and cardiovascular reflexes in conscious and anesthetized, young (4 months) and aged (18–20 months) αβγ−/− male mice. Aged mice displayed impaired respiratory responses to both hypoxia and hypercapnia when breathing activities were recorded in conscious animals using whole-body plethysmography. These animals were also found to be hypertensive from conscious blood pressure recordings, to have reduced pressor baroreflex gain under anesthesia, and showed reduced termination of both pressor and depressor reflexes. The present data demonstrate the importance of synuclein in the normal function of respiratory and cardiovascular reflexes during aging.

scholarly journals Expression of Toll-Like Receptors 2 and 4 and Related Cytokines in Patients with Hepatic Cystic and Alveolar Echinococcosis

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Tuerhongjiang Tuxun ◽  
Hai-Zhang Ma ◽  
Shadike Apaer ◽  
Heng Zhang ◽  
Amina Aierken ◽  
...  
Keyword(s):  
Alveolar Echinococcosis ◽  
Statistical Significance ◽  
Hepatic Tissue ◽  
Parasitic Infections ◽  
Control Group ◽  
Toll Like Receptors ◽  
Healthy Control ◽  
Human Cystic Echinococcosis ◽  
Concentration Levels

Several studies have demonstrated the important role of Toll-like receptors in various parasitic infections. This study aims to explore expression of Toll-like receptors (TLRs) and related cytokines in patients with human cystic echinococcosis (CE) and alveolar echinococcosis (AE). 78 subjects including AE group (N=28), CE group (N=22), and healthy controls (HC,N=28) were enrolled in this study. The mRNA expression levels of TLR2 and TLR4 in blood and hepatic tissue and plasma levels related cytokines were detected by using ELISA. Median levels of TLR2 mRNA in AE and CE groups were significantly elevated as compared with that in healthy control group. Median levels of TLR4 expression were increased in AE and CE. Plasma concentration levels of IL-5, IL-6, and IL-10 were slightly increased in AE and CE groups compared with those in HC group with no statistical differences (p>0.05). The IL-23 concentration levels were significantly higher in AE and CE groups than that in HC subjects with statistical significance. The increased expression of TLR2 and IL-23 might play a potential role in modulating tissue infiltrative growth of the parasite and its persistence in the human host.

Oxidative stress and reactive oxygen species: a review of their role in ocular disease

2017 ◽  
Vol 131 (24) ◽  
pp. 2865-2883 ◽  
Author(s):  
Lawson Ung ◽  
Ushasree Pattamatta ◽  
Nicole Carnt ◽  
Jennifer L. Wilkinson-Berka ◽  
Gerald Liew ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Cell Function ◽  
Physiological Role ◽  
Reactive Oxygen ◽  
Age Related Macular Degeneration ◽  
Current Evidence ◽  
Oxygen Species ◽  
Age Related

For many years, oxidative stress arising from the ubiquitous production of reactive oxygen species (ROS) has been implicated in the pathogenesis of various eye diseases. While emerging research has provided some evidence of the important physiological role of ROS in normal cell function, disease may arise where the concentration of ROS exceeds and overwhelms the body’s natural defence against them. Additionally, ROS may induce genomic aberrations which affect cellular homoeostasis and may result in disease. This literature review examines the current evidence for the role of oxidative stress in important ocular diseases with a view to identifying potential therapeutic targets for future study. The need is particularly pressing in developing treatments for conditions which remain notoriously difficult to treat, including glaucoma, diabetic retinopathy and age-related macular degeneration.

scholarly journals Loss of NHE8 expression impairs ocular surface function in mice

2015 ◽  
Vol 308 (1) ◽  
pp. C79-C87 ◽  
Author(s):  
Hua Xu ◽  
Yang Zhao ◽  
Jing Li ◽  
Mingwu Wang ◽  
Fangru Lian ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Ocular Surface ◽  
Gastric Gland ◽  
Physiological Role ◽  
Sodium Absorption ◽  
Marker Genes ◽  
Tear Production ◽  
Sodium Hydrogen Exchanger ◽  
Human And Mouse

Sodium/hydrogen exchanger (NHE) 8 is expressed at the apical membrane of the epithelial cells and plays important roles in neutral sodium absorption in the gastrointestinal tract and the kidney. It also has an important role in epithelial mucosal protection in the gastric gland and the intestine. Although NHE8 has broad tissue distribution, the precise location and the physiological role of NHE8 in the eye remain unknown. In the present study, we successfully detected the expression of NHE8 in the ocular surface by PCR and Western blot in human and mouse eyes. Immunohistochemistry staining located NHE8 protein at the plasma membrane of the epithelial cells in the conjunctiva, the cornea, and the lacrimal gland both in human and mouse. We also detected the expression of downregulated-in-adenoma (DRA, a Cl−/HCO3− transporter) in the ocular surface epithelial cells. Using NHE8−/− mouse model, we found that loss of NHE8 function resulted in reduced tear production and increased corneal staining. These NHE8−/− mice also showed increased expression of TNF-α and matrix metalloproteinase 9 (MMP9) genes. The expression of epithelial keratinization marker genes, small proline-rich protein 2h (Sprr2h) and transglutaminase 1 (Tgm1), were also increased in NHE8−/− eyes. Furthermore, DRA expression in NHE8−/− mice was reduced in the conjunctiva, the cornea, and the lacrimal glands in association with a reduction in conjunctival mucosal pH. Altered ocular surface function and reduced epithelial DRA expression in NHE8−/− mice suggest that the role of NHE8 in ocular surface tissue involve in tear production and ocular epithelial protection. This study reveals a potential novel mechanism of dry eye condition involving abnormal NHE8 function.

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