scholarly journals Allergic eye disease: blocking LTB4/C5 in vivo suppressed disease and Th2 & Th9 cells

Allergy ◽  
2021 ◽  
Author(s):  
Malihe Eskandarpour ◽  
Xiaozhe Zhang ◽  
Alessandra Micera ◽  
Sarah Zaher ◽  
Frank D.P. Larkin ◽  
...  
Keyword(s):  
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sean Swetledge ◽  
Renee Carter ◽  
Rhett Stout ◽  
Carlos E. Astete ◽  
Jangwook P. Jung ◽  
...  

AbstractPolymeric nanoparticles have been investigated as potential delivery systems for therapeutic compounds to address many ailments including eye disease. The stability and spatiotemporal distribution of polymeric nanoparticles in the eye are important regarding the practical applicability and efficacy of the delivery system in treating eye disease. We selected poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with lutein, a carotenoid antioxidant associated with eye health, as our model ophthalmic nanodelivery system and evaluated its stability when suspended in various conditions involving temperature and light exposure. We also assessed the ocular biodistribution of the fluorescently labeled nanoparticle vehicle when administered topically. Lutein-loaded nanoparticles were stable in suspension when stored at 4 °C with only 26% lutein release and no significant lutein decay or changes in nanoparticle morphology. When stored at 25 °C and 37 °C, these NPs showed signs of bulk degradation, had significant lutein decay compared to 4 °C, and released over 40% lutein after 5 weeks in suspension. Lutein-loaded nanoparticles were also more resistant to photodegradation compared to free lutein when exposed to ultraviolet (UV) light, decaying approximately 5 times slower. When applied topically in vivo, Cy5-labled nanoparticles showed high uptake in exterior eye tissues including the cornea, episcleral tissue, and sclera. The choroid was the only inner eye tissue that was significantly higher than the control group. Decreased fluorescence in all exterior eye tissues and the choroid at 1 h compared to 30 min indicated rapid elimination of nanoparticles from the eye.


2015 ◽  
Vol 56 (12) ◽  
pp. 7179 ◽  
Author(s):  
Ahmad Kheirkhah ◽  
Raheleh Rahimi Darabad ◽  
Andrea Cruzat ◽  
Amir Reza Hajrasouliha ◽  
Deborah Witkin ◽  
...  

2019 ◽  
Vol 94 (2) ◽  
Author(s):  
Kati Tormanen ◽  
Shaohui Wang ◽  
Homayon Ghiasi

ABSTRACT We recently reported that herpes simplex virus 1 (HSV-1) infection suppresses CD80 but not CD86 expression in vitro and in vivo. This suppression required the HSV-1 ICP22 gene. We also reported that overexpression of CD80 by HSV-1 exacerbated corneal scarring in BALB/c mice. We now show that this recombinant virus (HSV-CD80) expressed high levels of CD80 both in vitro in cultured rabbit skin cells and in vivo in infected mouse corneas. CD80 protein was detected on the surface of infected cells. The virulence of the recombinant HSV-CD80 virus was similar to that of the parental strain, and the replication of HSV-CD80 was similar to that of control virus in vitro and in vivo. Transcriptome analysis detected 75 known HSV-1 genes in the corneas of mice infected with HSV-CD80 or parental virus on day 4 postinfection. Except for significantly higher CD80 expression in HSV-CD80-infected mice, levels of HSV-1 gene expression were similar in corneas from HSV-CD80-infected and parental virus-infected mice. The number of CD8+ T cells was higher, and the number of CD4+ T cells was lower, in the corneas of HSV-CD80-infected mice than in mice infected with parental virus. HSV-CD80-infected mice displayed a transient increase in dendritic cells. Transcriptome analysis revealed mild differences in dendritic cell maturation and interleukin-1 signaling pathways and increased expression of interferon-induced protein with tetratricopeptide repeats 2 (Ifit2). Together, these results suggest that increased CD80 levels promote increased CD8+ T cells, leading to exacerbated eye disease in HSV-1-infected mice. IMPORTANCE HSV-1 ocular infections are the leading cause of corneal blindness. Eye disease is the result of a prolonged immune response to the replicating virus. HSV-1, on the other hand, has evolved several mechanisms to evade clearance by the host immune system. We describe a novel mechanism of HSV-1 immune evasion via ICP22-dependent downregulation of the host T cell costimulatory molecule CD80. However, the exact role of CD80 in HSV-1 immune pathology is not clear. In this study, we show that eye disease is independent of the level of HSV-1 replication and that viral expression of CD80 has a detrimental role in corneal scarring, likely by increasing CD8+ T cell recruitment and activation.


2019 ◽  
Vol 17 (2) ◽  
pp. 257-264 ◽  
Author(s):  
Agnė Žiniauskaitė ◽  
Symantas Ragauskas ◽  
Anita K. Ghosh ◽  
Rubina Thapa ◽  
Anne E. Roessler ◽  
...  

2019 ◽  
Vol 55 (91) ◽  
pp. 13657-13660
Author(s):  
Soonsil Hyun ◽  
Lan Li ◽  
Kyung Chul Yoon ◽  
Jaehoon Yu

The use of CPP, LK-3, increases the cell penetration of cyclosporine A (CsA) at nanomolar concentrations and therapeutic efficacy.


Metabolism ◽  
1997 ◽  
Vol 46 (5) ◽  
pp. 474-483 ◽  
Author(s):  
Latifa Elkhalil ◽  
Zouher Majd ◽  
Redouane Bakir ◽  
Oscar Perez-Mendez ◽  
Graciela Castro ◽  
...  

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Thomas John ◽  
Sean Tighe ◽  
Hosam Sheha ◽  
Pedram Hamrah ◽  
Zeina M. Salem ◽  
...  

Purpose. To evaluate the efficacy of self-retained cryopreserved amniotic membrane (CAM) in promoting corneal nerve regeneration and improving corneal sensitivity in dry eye disease (DED).Methods. In this prospective randomized clinical trial, subjects with DED were randomized to receive CAM (study group) or conventional maximum treatment (control). Changes in signs and symptoms, corneal sensitivity, topography, and in vivo confocal microscopy (IVCM) were evaluated at baseline, 1 month, and 3 months.Results. Twenty subjects (age 66.9 ± 8.9) were enrolled and 17 completed all follow-up visits. Signs and symptoms were significantly improved in the study group yet remained constant in the control. IVCM showed a significant increase in corneal nerve density in the study group (12,241 ± 5083 μm/mm2at baseline, 16,364 ± 3734 μm/mm2at 1 month, and 18,827 ± 5453 μm/mm2at 3 months,p=0.015) but was unchanged in the control. This improvement was accompanied with a significant increase in corneal sensitivity (3.25 ± 0.6 cm at baseline, 5.2 ± 0.5 cm at 1 month, and 5.6 ± 0.4 cm at 3 months,p<0.001) and corneal topography only in the study group.Conclusions. Self-retained CAM is a promising therapy for corneal nerve regeneration and accelerated recovery of the ocular surface health in patients with DED. The study is registered at clinicaltrials.gov with trial identifier:NCT02764814.


Author(s):  
Sam Henry ◽  
D. Shanaka Wijesinghe ◽  
Aidan Myers ◽  
Bridget T. McInnes

In this paper, we describe how we applied LBD techniques to discover lecithin cholesterol acyltransferase (LCAT) as a druggable target for cardiac arrest. We fully describe our process which includes the use of high-throughput metabolomic analysis to identify metabolites significantly related to cardiac arrest, and how we used LBD to gain insights into how these metabolites relate to cardiac arrest. These insights lead to our proposal (for the first time) of LCAT as a druggable target; the effects of which are supported by in vivo studies which were brought forth by this work. Metabolites are the end product of many biochemical pathways within the human body. Observed changes in metabolite levels are indicative of changes in these pathways, and provide valuable insights toward the cause, progression, and treatment of diseases. Following cardiac arrest, we observed changes in metabolite levels pre- and post-resuscitation. We used LBD to help discover diseases implicitly linked via these metabolites of interest. Results of LBD indicated a strong link between Fish Eye disease and cardiac arrest. Since fish eye disease is characterized by an LCAT deficiency, it began an investigation into the effects of LCAT and cardiac arrest survival. In the investigation, we found that decreased LCAT activity may increase cardiac arrest survival rates by increasing ω-3 polyunsaturated fatty acid availability in circulation. We verified the effects of ω-3 polyunsaturated fatty acids on increasing survival rate following cardiac arrest via in vivo with rat models.


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