Comparison of Aqueous Levels of Inflammatory Mediators Between Toxic Anterior Segment Syndrome and Endotoxin-Induced Uveitis Animal Models

Eom, Youngsub; Lee, Dong Y.eol; Kang, Bo; Heo, Jeong Hwa; Shin, Kyung Ho; Kim, Hyo M.yung; Song, Jong Suk

doi:10.1167/iovs.14-15051

Cited by 14 publications

(6 citation statements)

References 26 publications

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“…Consistently, the formation of keratic precipitates in the corneal endothelium is characteristic of uveitis [16]. Anterior uveitis involves infiltration of polymorphonuclear inflammatory cells, increased protein permeability, and upregulation of inflammatory cytokines in the aqueous humor [55,56]. In the present study, disrupted endothelial tight junction ZO-1, infiltrated inflammatory cells, and edema of the cornea were significantly induced by LPS treatment; however, these effects were suppressed by fucoxanthin treatment.…”

Section: Discussionsupporting

confidence: 76%

Protective Effects of Fucoxanthin Dampen Pathogen-Associated Molecular Pattern (PAMP) Lipopolysaccharide-Induced Inflammatory Action and Elevated Intraocular Pressure by Activating Nrf2 Signaling and Generating Reactive Oxygen Species

et al. 2021

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Inflammation and oxidative stress are closely related processes in the pathogenesis of various ocular diseases. Uveitis is a disorder of the uvea and ocular tissues that causes extreme pain, decreases visual acuity, and can eventually lead to blindness. The pharmacological functions of fucoxanthin, isolated from brown algae, induce a variety of therapeutic effects such as oxidative stress reduction and repression of inflammation reactions. However, the specific anti-inflammatory effects of fucoxanthin on pathogen-associated molecular pattern (PAMP) lipopolysaccharide-induced uveitis have yet to be extensively described. Therefore, the aim of present study was to investigate the anti-inflammatory effects of fucoxanthin on uveitis in rats. The results showed that fucoxanthin effectively enhanced the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) in ocular tissues. Furthermore, fucoxanthin significantly increased the ocular activities of superoxide dismutase and decreased the levels of malondialdehyde stimulated by PAMP-induced uveitis. Ocular hypertension and the levels of inflammatory cells and proinflammatory cytokine tumor necrosis factor-alpha in the aqueous humor were alleviated with fucoxanthin treatment. Consequently, compared to the observed effects in lipopolysaccharide groups, fucoxanthin treatment significantly preserved iris sphincter innervation and pupillary function. Additionally, PAMP-induced corneal endothelial disruption was significantly inhibited by fucoxanthin treatment. Overall, these findings suggest that fucoxanthin may protect against inflammation from PAMP-induced uveitis by promoting the Nrf2 pathway and inhibiting oxidative stress.

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Section: Discussionsupporting

confidence: 76%

Protective Effects of Fucoxanthin Dampen Pathogen-Associated Molecular Pattern (PAMP) Lipopolysaccharide-Induced Inflammatory Action and Elevated Intraocular Pressure by Activating Nrf2 Signaling and Generating Reactive Oxygen Species

et al. 2021

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“…It has been demonstrated that suppression of inflammation by steroids is related to their inhibitory effects on the production of inflammatory factors such as IL-6 and TNF-α. − Therefore, the levels of IL-6 and TNF-α in the inflammatory model were measured after treatment of the cells with different formulations; the results are shown in Figures c,d, respectively. Compared to the levels of IL-6 and TNF-α in cells that received no Dexp treatment (the LPS and HmA groups), the IL-6 and TNF-α levels in cells treated with Dexp (the free Dexp and Dexp@HmA groups) were markedly lower, indicating that Dexp has an ideal anti-inflammatory effect.…”

Section: Resultsmentioning

confidence: 99%

Evaluation of His₆-Metal Assemblies as a Drug Delivery Vehicle in the Treatment of Anterior Segment Disease Using a Corneal Inflammation Model

Wang

Luo

et al. 2020

ACS Biomater. Sci. Eng.

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Keratitis is a common ophthalmological disease and also a common cause of blindness (second only to cataracts). This disease is routinely treated by topical administration of dexamethasone sodium phosphate (Dexp). However, due to the presence of anatomical and physiological barriers, frequent administration is needed, often resulting in poor patient compliance and diverse side effects. In this work, Dexp was in situ encapsulated into a His 6 -metal assembly (HmA) to generate Dexp@ HmA, which was utilized in the ocular delivery of Dexp. The physicochemical properties of HmA and Dexp@HmA particles were characterized in detail using various techniques such as dynamic light scattering (DLS), scanning electron microscopy (SEM), and UV−vis spectroscopy. Compared to commercial Eudragi and reported PLGA nanoparticles, HmA showed higher encapsulation efficiency (EE%) and higher loading capacity (LC wt %) of Dexp. Dexp@HmA displayed pH-dependent release; after 33 days at pH 5.8, 6.5, and 7.2, 100%, 65%, and 42% of Dexp, respectively, had been released. In addition, HmA and Dexp@HmA showed low cytotoxicity to macrophages and to all common ocular cell types tested. The effect of Dexp@HmA on corneal inflammation was evaluated using in vitro and in vivo models. Our results demonstrate that Dexp@HmA is much superior to free Dexp in both in vitro and in vivo models. These positive results suggest that HmA may represent a promising candidate nanocarrier for the treatment of various diseases of the anterior segment of the eye.

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“…In line with this result in FP knock-out mice is the common knowledge that clinical use of cyclo-oxygenase inhibitors does not result in any meaningful change in intraocular pressure. This is despite the fact that all prostanoids are found endogenously present in the eye (27)(28)(29). It seems that under most circumstances prostanoids tending to either increase or decrease intraocular pressure are held in balance and that this balance is not altered, but rather nullified, by global inhibition of prostanoid biosynthesis.…”

Section: Pg 10mentioning

confidence: 99%

Gene deletion studies reveal a critical role for prostamide/prostaglandin F_2αsynthase in prostamide F_2αformation

Woodward

et al. 2020

Preprint

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Prostamide/prostaglandin F synthase (PM/PGFS) is an enzyme with very narrow substrate specificity and is dedicated to the biosynthesis of prostamide and prostaglandin F2α. The importance of this enzyme, pg. 2 relative to the aldoketoreductase (AKR) series, in providing functional tissue prostamide F2α levels was determined by creating a line of PM/PGFS gene deleted mice. Deletion of the gene encoding PM/PGFS (fam213b) was accomplished by a two exon disruption. Prostamide F2α levels in WT and PM/PGFS KO mice were determined by LC/MS/MS. Intraocular pressure was measured by tonometry and outflow facility was measured by the iPerfusion method in enucleated mouse eyes. Deletion of fam213b had no observed effect on behavior, appetite, or fertility. Intraocular pressure was significantly elevated by approximately 4 mmHg in PM/PGFS KO mice compared to littermate WT mice. No effect on pressure dependent outflow facility occurred, which is consistent with the typically reported prostanoid effect of increasing outflow through the unconventional pathway. The elevation of intraocular pressure caused by deletion of the gene encoding the PM/PGFS enzyme likely results from a diversion of the endoperoxide precursor pathway to provide increased levels of those prostanoids that raise intraocular pressure, namely prostaglandin D2 (PGD2), thromboxane A2 (TxA2). It follows that PM/PGFS may serve an important regulatory role in the eye by providing PGF2α and prostamide F2α to constrain the influence of those prostanoids that raise intraocular pressure. Keywords(a) Expertise key words: prostaglandins, eye, animal models, enzymology, gene expression (b) Free-form key words prostamide/prostaglandin F synthase, fam213b, prostamide F2α, prostaglandin F2α, , intraocular pressure, 13). More recently, a much more substrate specific enzyme and a member of the thioredoxin-like superfamily was discovered and was designated prostamide/prostaglandin F synthase (14,15), PM/PGFS, fam213. This enzyme facilitates a more restricted and targeted formation of PGF2α and prostamide F2α and thereby conferring tighter control of regulatory function(s). Gene deletion is a classical approach for discovering biological functions and the first results of these studies are presented herein, together with the methodology for creating prostamide/prostaglandin F synthase (fam213) knock-out mice. Given the importance of PGF2α and prostamide F2α in the treatment of glaucoma, these present studies focused on regulation of intraocular pressure. pg. 4Methods Creation of prostamide/prostaglandin F synthase (fam213) knock-out mice.The prostamide/prostaglandin F synthase (PM/PGFS) knock-out mouse was generated using the RENKA embryonic stem (ES) cell line, derived from C57BL/6N mice (16). To construct a PM/PGFS targeting vector, a 990 bp DNA fragment carrying exons 2 and 3, containing the enzyme active site of PM/PGFS, was amplified by PCR, and inserted into the targeting vector as described previously (17). In this clone, a DNA fragment of a PGK promoter-driven neo-poly (A...

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Comparison of Aqueous Levels of Inflammatory Mediators Between Toxic Anterior Segment Syndrome and Endotoxin-Induced Uveitis Animal Models

Abstract: Prostaglandin E2 and TNF-α in aqueous humor seem to be regulated differently in animal models of TASS and EIU. However, dexamethasone pretreatment improved the clinical findings and inhibited the increases in PGE2 and TNF-α in both animal models.

Cited by 14 publications

References 26 publications

Protective Effects of Fucoxanthin Dampen Pathogen-Associated Molecular Pattern (PAMP) Lipopolysaccharide-Induced Inflammatory Action and Elevated Intraocular Pressure by Activating Nrf2 Signaling and Generating Reactive Oxygen Species

Protective Effects of Fucoxanthin Dampen Pathogen-Associated Molecular Pattern (PAMP) Lipopolysaccharide-Induced Inflammatory Action and Elevated Intraocular Pressure by Activating Nrf2 Signaling and Generating Reactive Oxygen Species

Evaluation of His₆-Metal Assemblies as a Drug Delivery Vehicle in the Treatment of Anterior Segment Disease Using a Corneal Inflammation Model

Gene deletion studies reveal a critical role for prostamide/prostaglandin F_2αsynthase in prostamide F_2αformation

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Comparison of Aqueous Levels of Inflammatory Mediators Between Toxic Anterior Segment Syndrome and Endotoxin-Induced Uveitis Animal Models

Abstract: Prostaglandin E2 and TNF-α in aqueous humor seem to be regulated differently in animal models of TASS and EIU. However, dexamethasone pretreatment improved the clinical findings and inhibited the increases in PGE2 and TNF-α in both animal models.

Cited by 14 publications

References 26 publications

Protective Effects of Fucoxanthin Dampen Pathogen-Associated Molecular Pattern (PAMP) Lipopolysaccharide-Induced Inflammatory Action and Elevated Intraocular Pressure by Activating Nrf2 Signaling and Generating Reactive Oxygen Species

Protective Effects of Fucoxanthin Dampen Pathogen-Associated Molecular Pattern (PAMP) Lipopolysaccharide-Induced Inflammatory Action and Elevated Intraocular Pressure by Activating Nrf2 Signaling and Generating Reactive Oxygen Species

Evaluation of His6-Metal Assemblies as a Drug Delivery Vehicle in the Treatment of Anterior Segment Disease Using a Corneal Inflammation Model

Gene deletion studies reveal a critical role for prostamide/prostaglandin F2αsynthase in prostamide F2αformation

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Evaluation of His₆-Metal Assemblies as a Drug Delivery Vehicle in the Treatment of Anterior Segment Disease Using a Corneal Inflammation Model

Gene deletion studies reveal a critical role for prostamide/prostaglandin F_2αsynthase in prostamide F_2αformation