sirolimus has been researched along with Dry-Eye-Syndromes* in 7 studies
1 review(s) available for sirolimus and Dry-Eye-Syndromes
1 trial(s) available for sirolimus and Dry-Eye-Syndromes
6 other study(ies) available for sirolimus and Dry-Eye-Syndromes
| Article | Year |
|---|---|
Insulin-like growth factor binding protein-3 mediates hyperosmolar stress-induced mitophagy through the mechanistic target of rapamycin.
Hyperosmolarity of the ocular surface triggers inflammation and pathological damage in dry eye disease (DED). In addition to a reduction in quality of life, DED causes vision loss and when severe, blindness. Mitochondrial dysfunction occurs as a consequence of hyperosmolar stress. We have previously reported on a role for the insulin-like growth factor binding protein-3 (IGFBP-3) in the regulation of mitochondrial ultrastructure and metabolism in mucosal surface epithelial cells; however, this appears to be context-specific. Due to the finding that IGFBP-3 expression is decreased in response to hyperosmolar stress in vitro and in an animal model of DED, we next sought to determine whether the hyperosmolar stress-mediated decrease in IGFBP-3 alters mitophagy, a key mitochondrial quality control mechanism. Here we show that hyperosmolar stress induces mitophagy through differential regulation of BNIP3L/NIX and PINK1-mediated pathways. In corneal epithelial cells, this was independent of p62. The addition of exogenous IGFBP-3 abrogated the increase in mitophagy. This occurred through regulation of mTOR, highlighting the existence of a new IGFBP-3-mTOR signaling pathway. Together, these findings support a novel role for IGFBP-3 in mediating mitochondrial quality control in DED and have broad implications for epithelial tissues subject to hyperosmolar stress and other mitochondrial diseases. Topics: Animals; Dry Eye Syndromes; Humans; Insulin-Like Growth Factor Binding Protein 3; Mitophagy; Quality of Life; Sirolimus; TOR Serine-Threonine Kinases | 2023 |
Rapamycin Eyedrops Increased CD4
Dry eye disease (DED), one of the most prevalent conditions among the elderly, is a chronic inflammatory disorder that disrupts tear film stability and causes ocular surface damage. Aged C57BL/6J mice spontaneously develop DED. Rapamycin is a potent immunosuppressant that prolongs the lifespan of several species. Here, we compared the effects of daily instillation of eyedrops containing rapamycin or empty micelles for three months on the aged mice. Tear cytokine/chemokine profile showed a pronounced increase in vascular endothelial cell growth factor-A (VEGF-A) and a trend towards decreased concentration of Interferon gamma (IFN)-γ in rapamycin-treated groups. A significant decrease in inflammatory markers in the lacrimal gland was also evident ( Topics: Aging; Animals; Autophagy-Related Protein-1 Homolog; CD4 Antigens; Cell Lineage; Conjunctiva; Cornea; Disease Models, Animal; Dry Eye Syndromes; Forkhead Transcription Factors; Goblet Cells; Humans; Inflammation; Interferon-gamma; Leukocyte Common Antigens; Mice; Ophthalmic Solutions; Sirolimus; Tears; Vascular Endothelial Growth Factor A | 2020 |
Autophagy Activation Protects Ocular Surface from Inflammation in a Dry Eye Model In Vitro.
Inflammation is the main pathophysiology of dry eye, characterized by tear film instability and hyperosmolarity. The aim of this study was to investigate the association of inflammation and cellular autophagy using an in vitro dry eye model with primary cultured human corneal epithelial cells (HCECs). Primary HCECs cultured with fresh limbal explants from donors were switched to a hyperosmotic medium (450 mOsM) by adding sodium chloride into the culture medium. We observed the stimulated inflammatory mediators, TNF-α, IL-1β, IL-6 and IL-8, as well as the increased expression of autophagy related genes, Ulk1, Beclin1, Atg5 and LC3B, as evaluated by RT-qPCR and ELISA. The immunofluorescent staining of LC3B and Western blotting revealed the activated autophagosome formation and autophagic flux, as evidenced by the increased LC3B autophagic cells with activated Beclin1, Atg5, Atg7 and LC3B proteins, and the decreased levels of P62 protein in HCECs. Interestingly, the autophagy activation was later at 24 h than inflammation induced at 4 h in HCECs exposed to 450 mOsM. Furthermore, application of rapamycin enhanced autophagy activation also reduced the inflammatory mediators and restored cell viability in HCECs exposed to the hyperosmotic medium. Our findings for the first time demonstrate that the autophagy activation is a late phase response to hyperosmotic stress, and is enhanced by rapamycin, which protects HCECs by suppressing inflammation and promoting cells survival, suggesting a new therapeutic potential to treat dry eye diseases. Topics: Adolescent; Adult; Aged; Autophagosomes; Autophagy; Cell Survival; Cells, Cultured; Cytoprotection; Dry Eye Syndromes; Epithelial Cells; Epithelium, Corneal; Humans; Inflammation; Inflammation Mediators; Middle Aged; Models, Biological; Osmotic Pressure; Sirolimus; Time Factors; Young Adult | 2020 |
Effect of Rapamycin Microspheres in Sjögren Syndrome Dry Eye: Preparation and Outcomes.
Topics: Animals; Conjunctiva; Delayed-Action Preparations; Disease Models, Animal; Dry Eye Syndromes; Female; Immunosuppressive Agents; Mice; Microspheres; Sirolimus; Sjogren's Syndrome | 2019 |
Rapamycin Rescues Endoplasmic Reticulum Stress-Induced Dry Eye Syndrome in Mice.
To investigate whether rapamycin protects tear production and the ocular surface during endoplasmic reticulum (ER) stress-induced dry eye syndrome in mice.. Tunicamycin was injected intraperitoneally in BALB/c mice without or with rapamycin (TM or RM5 group). Peritoneal injection of PBS performed in vehicle group. Group without injection served as control. Blinking rate, fluorescein staining score (FSS), and phenol red thread tear production test were measured at 4 days, 1 week, and 2 weeks after treatment. Levels of inflammatory and angiogenic cytokines were measured by ELISA.. Blinking rate and FSS were elevated, and tear production was decreased in TM group compared with controls (P < 0.05 for all), which was ameliorated by rapamycin at 1 and 2 weeks. Levels of inflammatory and angiogenic cytokines in the cornea and lacrimal glands were higher in the TM group than controls, and lower in the RM5 group than the TM group at 1 and 2 weeks (P < 0.05 for all).. Rapamycin protected tear production and the ocular surface against this dry eye syndrome by ameliorating ER stress-induced vascular damage and inflammation of lacrimal glands and the ocular surface. Topics: Animals; Anti-Bacterial Agents; Blinking; Blotting, Western; Cytokines; Dry Eye Syndromes; Endoplasmic Reticulum Stress; Enzyme-Linked Immunosorbent Assay; Eye Proteins; Female; Immunosuppressive Agents; Injections, Intraperitoneal; Lacrimal Apparatus; Mice; Mice, Inbred BALB C; Sirolimus; Tears; Tunicamycin | 2019 |
TRI Microspheres prevent key signs of dry eye disease in a murine, inflammatory model.
Dry eye disease (DED) is a highly prevalent, ocular disorder characterized by an abnormal tear film and ocular surface. Recent experimental data has suggested that the underlying pathology of DED involves inflammation of the lacrimal functional unit (LFU), comprising the cornea, conjunctiva, lacrimal gland and interconnecting innervation. This inflammation of the LFU ultimately results in tissue deterioration and the symptoms of DED. Moreover, an increase of pathogenic lymphocyte infiltration and the secretion of pro-inflammatory cytokines are involved in the propagation of DED-associated inflammation. Studies have demonstrated that the adoptive transfer of regulatory T cells (Tregs) can mediate the inflammation caused by pathogenic lymphocytes. Thus, as an approach to treating the inflammation associated with DED, we hypothesized that it was possible to enrich the body's own endogenous Tregs by locally delivering a specific combination of Treg inducing factors through degradable polymer microspheres (TRI microspheres; TGF-β1, Rapamycin (Rapa), and IL-2). This local controlled release system is capable of shifting the balance of Treg/T effectors and, in turn, preventing key signs of dry eye disease such as aqueous tear secretion, conjunctival goblet cells, epithelial corneal integrity, and reduce the pro-inflammatory cytokine milieu in the tissue. Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Delayed-Action Preparations; Disease Models, Animal; Dry Eye Syndromes; Female; Inflammation; Interleukin-2; Lacrimal Apparatus; Mice, Inbred BALB C; Microspheres; Polymers; Sirolimus; T-Lymphocytes, Regulatory; Transforming Growth Factor beta1 | 2017 |