Cathepsin S is a novel target for age-related dry eye

Abstract Background. Long noncoding RNAs (lncRNAs) have been indicated that participate in inflammatory diaeases and age related diseases by regulating physiological and pathological processes directly or indirectly. Evidences have indicated lncRNAs might be involving in dry eye disease which can cause pathological changes of cornea and conjunctiva in ocular surface though inflammatory response. KCNQ1OT1 is a novel lncRNA, whose function remains totally unclear.Methods. qRT-PCR was performed to detect the expression of KCNQ1OT1, miR-214 and inflammasome-related genes NLRP3, caspase1 and IL-1β. Western blotting was carried out to detect inflammasome-related markers. The dry eye disease (DED) model was set up by scopolamine hydrobromide though subcutaneous injection. Bioinformatics was used to predict and validate the interaction between KCNQ1OT1 and miR-214 as well caspase1 and miR-214.Results. KCNQ1OT1 was significantly up-regulated during the process of DED while miR-214 was contrarily down-regulated. Knockdown of KCNQ1OT1 promoted cornea epithelial cells migration and down-regulated inflammasome-related genes. It was also confirmed that KCNQ1OT1 directly interacted with miR-214. Meanwhile, miR-214 could bind to 3'UTR of caspase1 and therefore inhibited its expression. Furthermore, co-transfection of miR-214 inhibitor could rescue the down-regulation of cell migration induced by KCNQ1OT1 knockdown.

Download Full-text

“DRY EYE” SYNDROME IN THE CHILDREN: CURRENT POSSIBILITIES FOR DIAGNOSTICS AND TREATMENT (THE GUIDELINES FOR PRACTITIONERS)

Russian Pediatric Ophthalmology ◽

10.18821/1993-1859-2017-12-2-73-8 ◽

2017 ◽

Vol 12 (2) ◽

pp. 73-81

Author(s):

Vladimir Vsevolodovich Brzheskiy

Keyword(s):

Dry Eye ◽

Specific Treatment ◽

Diagnostic Value ◽

Dry Eye Syndrome ◽

Eye Drops ◽

Congenital Diseases ◽

Age Related ◽

Ready Availability ◽

Extensive Introduction ◽

The One

Purpose. The «dry eye» syndrome in the children occurs much less frequently than in the adults, but it is often diagnosed in the contact lens wearers, the subjects presenting with the computer vision syndrome, and in the children with glaucoma (especially against the background of the instillations of the hypotensive eye drops with a preservative), chronic uveitis, diabetes mellitus, and certain congenital diseases of the eyelids and lacrimal glands. On the one hand, the pathology being considered is very similar in the children and adults in terms of etiology and pathogenesis, but on the other hand, it has a number of peculiar age-related features as regards the clinical course and the modes of treatment of this disease specific for either group of the patients. To begin with, the children very rarely complain about this condition and exhibit the relatively mild objective manifestations of the disorder (xerosis), with the exception of its extremely severe forms. Finally, the specific treatment of the children suffering from the «dry eye» syndrome with the majority of the medications currently available for the purpose is hampered by the age-related limitations whereas they are extensively and successfully used for the treatment of the same condition in the adults. Accordingly, the approaches to diagnostics of the «dry eye» syndrome in the children differ from those in the adults. Specifically, questioning of the children and their parents (to evaluate the complaints and the medical history) is of negligible diagnostic value whereas in the adults this approach provides the most valuable diagnostic information. In addition, it is very difficult to conduct a series of diagnostic tests in the young children due to their restless behavior during the examination. Conclusion. At the same time, there are currently the considerable opportunities for the diagnostics and treatment of the «dry eye» syndrome due to the ready availability of “artificial tear” preparations and stimulators of regeneration as well as the possibility of lacrimal duct obturation. It implies the necessity of the more extensive introduction of these modalities into the pediatric ophthalmological practiced.

Download Full-text

Integrated analysis of microRNA and mRNA expression profiling identifies BAIAP3 as a novel target of dysregulated hsa-miR-1972 in age-related white matter lesions

Aging ◽

10.18632/aging.202562 ◽

2021 ◽

Vol 13 (3) ◽

pp. 4674-4695

Author(s):

Wen-Qing Huang ◽

Qing Lin ◽

Shuai Chen ◽

Lixiang Sun ◽

Qingjie Chen ◽

...

Keyword(s):

White Matter ◽

Mrna Expression ◽

Expression Profiling ◽

White Matter Lesions ◽

Integrated Analysis ◽

Age Related ◽

Novel Target ◽

Mrna Expression Profiling

Download Full-text

Mitochondria and Calcium Homeostasis: Cisd2 as a Big Player in Cardiac Ageing

International Journal of Molecular Sciences ◽

10.3390/ijms21239238 ◽

2020 ◽

Vol 21 (23) ◽

pp. 9238

Author(s):

Chi-Hsiao Yeh ◽

Yi-Ju Chou ◽

Cheng-Heng Kao ◽

Ting-Fen Tsai

Keyword(s):

Energy Metabolism ◽

Cardiac Dysfunction ◽

Molecular Mechanisms ◽

Dynamic Control ◽

Basic Research ◽

Human Populations ◽

Age Related ◽

Novel Target ◽

High Level ◽

New Evidence

The ageing of human populations has become a problem throughout the world. In this context, increasing the healthy lifespan of individuals has become an important target for medical research and governments. Cardiac disease remains the leading cause of morbidity and mortality in ageing populations and results in significant increases in healthcare costs. Although clinical and basic research have revealed many novel insights into the pathways that drive heart failure, the molecular mechanisms underlying cardiac ageing and age-related cardiac dysfunction are still not fully understood. In this review we summarize the most updated publications and discuss the central components that drive cardiac ageing. The following characters of mitochondria-related dysfunction have been identified during cardiac ageing: (a) disruption of the integrity of mitochondria-associated membrane (MAM) contact sites; (b) dysregulation of energy metabolism and dynamic flexibility; (c) dyshomeostasis of Ca2+ control; (d) disturbance to mitochondria–lysosomal crosstalk. Furthermore, Cisd2, a pro-longevity gene, is known to be mainly located in the endoplasmic reticulum (ER), mitochondria, and MAM. The expression level of Cisd2 decreases during cardiac ageing. Remarkably, a high level of Cisd2 delays cardiac ageing and ameliorates age-related cardiac dysfunction; this occurs by maintaining correct regulation of energy metabolism and allowing dynamic control of metabolic flexibility. Together, our previous studies and new evidence provided here highlight Cisd2 as a novel target for developing therapies to promote healthy ageing

Download Full-text

Age-Related Dry Eye Lactoferrin and Lactobionic Acid

Ophthalmic Research ◽

10.1159/000489093 ◽

2018 ◽

Vol 60 (2) ◽

pp. 94-99 ◽

Cited By ~ 5

Author(s):

Dario Rusciano ◽

Salvatore Pezzino ◽

Melania Olivieri ◽

Martina Cristaldi ◽

Caterina Gagliano ◽

...

Keyword(s):

Dry Eye ◽

Lactobionic Acid ◽

Age Related

Download Full-text

Mitochondria-Targeted Antioxidant SkQ1 Prevents Anesthesia-Induced Dry Eye Syndrome

Oxidative Medicine and Cellular Longevity ◽

10.1155/2017/9281519 ◽

2017 ◽

Vol 2017 ◽

pp. 1-17 ◽

Cited By ~ 17

Author(s):

Evgeni Yu. Zernii ◽

Olga S. Gancharova ◽

Viktoriia E. Baksheeva ◽

Marina O. Golovastova ◽

Ekaterina I. Kabanova ◽

...

Keyword(s):

Oxidative Stress ◽

Antioxidant Activity ◽

General Anesthesia ◽

Dry Eye ◽

Ocular Surface ◽

Protective Action ◽

Dry Eye Syndrome ◽

Clinical State ◽

Ocular Surgery ◽

Age Related

Dry eye syndrome (DES) is an age-related condition increasingly detected in younger people of risk groups, including patients who underwent ocular surgery or long-term general anesthesia. Being a multifactorial disease, it is characterized by oxidative stress in the cornea and commonly complicated by ocular surface inflammation. Polyetiologic DES is responsive to SkQ1, a mitochondria-targeted antioxidant suppressing age-related changes in the ocular tissues. Here, we demonstrate safety and efficacy of topical administration of SkQ1 at a dosage of 7.5 μM for the prevention of general anesthesia-induced DES in rabbits. The protective action of SkQ1 improves clinical state of the ocular surface by inhibiting apoptotic and prenecrotic changes in the corneal epithelium. The underlying mechanism involves the suppression of the oxidative stress supported by the stimulation of intrinsic antioxidant activity and the activity of antioxidant enzymes, foremost glutathione peroxidase and glutathione reductase, in the cornea. Furthermore, SkQ1 increases antioxidant activity and stability of the tear film and produces anti-inflammatory effect exhibited as downregulation of TNF-α and IL-6 and pronounced upregulation of IL-10 in tears. Our data suggest novel features of SkQ1 and point to its feasibility in patients with DES and individuals at risk for the disease including those subjected to general anesthesia.

Download Full-text