scholarly journals Rapamycin Eyedrops Increased CD4+Foxp3+ Cells and Prevented Goblet Cell Loss in the Aged Ocular Surface

2020 ◽  
Vol 21 (23) ◽  
pp. 8890
Author(s):  
Claudia M. Trujillo-Vargas ◽  
Shallu Kutlehria ◽  
Humberto Hernandez ◽  
Rodrigo G. de Souza ◽  
Andrea Lee ◽  
...  

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 (IFN-γ, IL-12, CIITA and Ctss); this was accompanied by slightly diminished Unc-51 Like Autophagy Activating Kinase 1 (ULK1) transcripts. In the lacrimal gland and draining lymph nodes, we also observed a significant increase in the CD45+CD4+Foxp3+ cells in the rapamycin-treated mice. More importantly, rapamycin eyedrops increased conjunctival goblet cell density and area compared to the empty micelles. Taken together, evidence from these studies indicates that topical rapamycin has therapeutic efficacy for age-associated ocular surface inflammation and goblet cell loss and opens the venue for new investigations on its role in the aging process of the eye.

2015 ◽  
Vol 56 (12) ◽  
pp. 7545 ◽  
Author(s):  
Stephen C. Pflugfelder ◽  
Cintia S. De Paiva ◽  
Quianta L. Moore ◽  
Eugene A. Volpe ◽  
De-Quan Li ◽  
...  
Keyword(s):  

2010 ◽  
Vol 63 (11-12) ◽  
pp. 793-800 ◽  
Author(s):  
Gordana Stankovic-Babic ◽  
Gordana Zlatanovic ◽  
Jasmina Djordjevic-Jocic ◽  
Sonja Cekic ◽  
Milena Vujanovic

Introduction. Dry eye disease or dysfunctional tear syndrome is among the most frequently established diagnoses in ophthalmology. It can be defined as a disorder of the tear film resulting in changes in the ocular surface. Mechanisms in development of dry eye disease. There are many factors causing dry eye and they can be related to deficiency in any of the components of the tear film. It has been suggested that dry eye is an inflammatory disorder that affects the ocular surface and lacrimal gland. Inflammation is the most important mechanism of corneal and conjunctival cell damage, which is responsible for the symptoms and signs of ocular surface pathology. Hormonal imbalance (particularly androgens), neural dysfunction, increased levels of pro-inflammatory cytokines and loss of immune homeostasis of the lacrimal gland and ocular surface could be possible mechanisms in the pathogenesis of dry eye disease. Discussion. The aim of this paper was to review the advances in the pathogenesis and management of the dry eye disease. The appropriate dry eye treatment presupposes knowledge of all existing pharmacologic and non-pharmacologic therapeutic modalities. The mainstay of therapy is still artificial tears, with anti-inflammatory therapy and punctual occlusion therapy as second and third line therapies.


JCI Insight ◽  
2018 ◽  
Vol 3 (3) ◽  
Author(s):  
Byung Yi Ko ◽  
Yangyan Xiao ◽  
Flavia L. Barbosa ◽  
Cintia S. de Paiva ◽  
Stephen C. Pflugfelder

2019 ◽  
Vol 44 (2) ◽  
pp. 82
Author(s):  
Maretha Amrayni ◽  
Elsa Gustianty ◽  
Susi Heryati ◽  
Andika Prahasta ◽  
Maula Rifada ◽  
...  

Introduction : The longterm use of topical antiglaucoma might cause ocular surface instability due to active substance or preservative used. Impression cytology examination may reveal superficial epithelial cells on conjunctiva and cornea, including goblet cells. Goblet cell density decrease is the most important parameter on evaluation of ocular surface disorder. Objective : This study was to understand ocular surface remodeling due to active substance of topical antiglaucoma with impression cytology examination among the patient prior and 3 months after therapy. Methods : This was a randomized controlled trial study with single blind masking. A total of 45 eyes from 31 patients were used as subject and distributed onto three groups treatment, which were timolol maleat 0.5%, latanoprost 0.005%, and latanoprost-timolol maleat fixed combination. All topical antiglaucoma in this study were preservative free. Result : There were differences between 3 groups in goblet cells density after 3 months therapy (p=0,030). Goblet cell density in timolol group was lower than latanoprost (p=0,041) and fixed combination (p=0,045). There was no significantly difference between 3 groups in conjunctival epithelial metaplasia degree (p=0,706) and cell to cell contact degree in corneal epithelial cells (p=0.66) after 3 months therapy. Conjunctival epithelial metaplasia degree were increased among group of timolol (p=0,008) and fixed combination (p=0,046). Conclusion : Timolol maleat 0,5% caused lower goblet cell density after 3 months therapy compare with latanoprost and fixed combination. There was no significantly difference in conjunctival epithelial metaplasia and cell to cell contact degree in corneal epithelial cells among these glaucoma treatment groups.


2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
Saveria Pastore ◽  
Liudmila Korkina

The skin is permanently exposed to physical, chemical, and biological aggression by the environment. In addition, acute and chronic inflammatory events taking place in the skin are accompanied by abnormal release of pro-oxidative mediators. In this paper, we will briefly overview the homeostatic systems active in the skin to maintain the redox balance and also to counteract abnormal oxidative stress. We will concentrate on the evidence that a local and/or systemic redox dysregulation accompanies the chronic inflammatory disorder events associated to psoriasis, contact dermatitis, and atopic dermatitis. We will also discuss the fact that several well-established treatments for the therapy of chronic inflammatory skin disorders are based on the application of strong physical or chemical oxidants onto the skin, indicating that, in selected conditions, a further increase of the oxidative imbalance may lead to a beneficial outcome.


2021 ◽  
pp. 116-123
Author(s):  
Roald Vissing-Uhre ◽  
Alastair Hansen ◽  
Susanne Frevert ◽  
Ditte Hansen

Kimura disease (KD) is a chronic, inflammatory disorder with slowly developing subcutaneous tumor-like swellings, often occurring in the head and neck region. KD is diagnosed based on histology, elevated levels of immunoglobulin type E, and increased peripheral eosinophil granulocytes. KD may coexist with glomerular renal diseases, and this case report is based on a patient with KD-associated membranous nephropathy. Patients with membranous nephropathy without KD have demonstrated responsiveness to treatment with monoclonal anti-CD20 antibodies. This case report is the first to investigate the effect of rituximab treatment in a patient with KD-associated membranous nephropathy. A 30-year-old Italian man living in Denmark was diagnosed with Kimura’s disease based on subcutaneous nodules with eosinophil angiolymphoid hyperplasia. The patient was admitted to the hospital due to nephrotic syndrome. Serology showed eosinophil granulocytosis and negative PLA2-receptor antibody. Renal biopsy showed membranous nephropathy, and the patient was treated with systemic methylprednisolone followed by cyclosporin and then cyclophosphamide with only partial remission. Ultimately, treatment with intravenous rituximab was initiated, which resulted in overall remission and no nephrotic relapses at 30 months of follow-up. Thus, intravenous rituximab effectively decreased proteinuria and prevented nephrotic relapses in a patient with treatment-refractory membranous nephropathy due to KD.


2021 ◽  
Vol 13 ◽  
pp. 1759720X2110069
Author(s):  
Yanpan Gao ◽  
Yanyu Chen ◽  
Lun Wang ◽  
Chen Li ◽  
Wei Ge

Objective: Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare chronic inflammatory disorder and the underlying pathogenesis is unclear. In this study, 88 SAPHO patients and 118 healthy controls were recruited to investigate the role of serum-derived extracellular vesicles (SEVs) in SAPHO syndrome. Methods: Quantitative proteomics was applied for SEVs proteome identification, and ELISA and Western blotting was performed to verify the results of mass spectrum data. In vitro osteoclastogenesis and osteogenesis assay was used to confirm the effects of SEVs on bone metabolism. Results: Tandem mass tagging-based quantitative proteomic analysis of SAPHO SEVs revealed differential expressed proteins involved in bone metabolism. Of these, serum amyloid A-1 (SAA1) and C-reactive protein (CRP) were upregulated. Higher SAA1 levels in SAPHO patients were confirmed by ELISA. In addition, SAA1 levels were positively correlated with CRP, an inflammatory marker related to the condition of patients. In vitro celluler studies confirmed that SAPHO SEVs inhibited osteoclastogenesis in patients mainly in the active phase of the disease. Further analysis demonstrated that Nucleolin was upregulated in osteoclasts of active-phase patients under SAPHO SEVs stimulation. Conclusion: In this study, we identified SAA1 as an additional inflammation marker that can potentially assist the diagnosis of SAPHO syndrome, and speculated that Nucleolin is a key regulator of osteoclastogenesis in active-phase patients.


2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Arash Mollaeian ◽  
Jingjing Chen ◽  
Nina N. Chan ◽  
Gregory A. Nizialek ◽  
Christopher J. Haas

Abstract Background Adult onset Still’s disease (AOSD) is a rare inflammatory disorder that classically presents with high spiking fevers, evanescent rash, and arthritis. The diagnosis is one of exclusion and can be further complicated by atypical presentations, particularly in elderly patients in whom AOSD is very rare. Case presentation A case of AOSD in a 73-year-old woman with a non-classic presentation, leading to delayed diagnosis and management, is presented along with a review of the English literature for AOSD cases in elderly people over 70 years of age. Thirty nine case reports and series were identified and the current case was added, totaling 42 individual cases. Significant findings included a four-times higher prevalence in females, a higher prevalence of macrophage activation syndrome despite lower mortality, the presence of pruritic rash in almost one fifth of the cases, and high prevalence of delayed diagnosis. Conclusions AOSD in the elderly may vary from the classic criteria described in the medical literature and may lead to delayed diagnosis and management. Further evaluation and better characterization of AOSD in the elderly remains an area of interest.


2008 ◽  
Vol 86 (2) ◽  
pp. 403-411 ◽  
Author(s):  
D.F. Yu ◽  
Y. Chen ◽  
J.M. Han ◽  
H. Zhang ◽  
X.P. Chen ◽  
...  

2011 ◽  
Vol 26 (S2) ◽  
pp. 229-229
Author(s):  
F. Maner ◽  
Ö. Şahmelikoğlu ◽  
Ö. Hısım ◽  
H. Özhan ◽  
H. Sarıahmetoğlu ◽  
...  

IntroductionBehcet's Syndrome is a chronic inflammatory disorder of unknown etiology, characterized by aphthous lesions and recurrent ulceration of the mouth, genitals and uveitis.ObjectivesThe central nervous system is involved in about 20% of cases.AimsOnly few reports deal with affective symptoms associated with Behcet's syndrome.MethodsWe report a case of a 43 year old male with Neuro-Behcet's Syndrome that presents with a psychotic manic attack. He developed Behcet's Syndrome at the age of 23, with recurrent uveitis and aphthous lesions in the mouth, painful ulcers in the genitalia and erythema nodosum. HLA-B 5 was positive.ResultsHe was treated with azothioprine 150 mg/day for 13 years and prednole 100 mg/day during uveitis attacts for a week. At the age of 37 a sudden occurrence of right hemiparesia due to cerebrovascular accidence salicylic acid 100mg/day, siclosporine 150 mg/day, piracetame 1600mg/day were administered. He presented to psychiatry clinic in manic episode with euphoric mood, psychomotor agitation, talkativeness, decreased need for sleep, excessive buying and he had an unrealistical thought that he was a player of a famous soccer team. He was diagnosed as bipolar I disorder, according to DSM-IV. This was the patient's first admission and the symptoms which were continuing for 6 years exaggerated during uveitis attacks.Psychiatric examination releaved that increaced psychomotor activity, hypomaniac affect, amount and affect speed of speech affect, increased associations, grandiose delusions.ConclusionThere are a few reports dealing with bipolar disorder as an entity related to Behcet's syndrome.


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