Browse
Submit Data
Databases
API
Help

Dataset Information

27 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Increased aqueous autotaxin and lysophosphatidic acid levels are potential prognostic factors after trabeculectomy in different types of glaucoma.

ABSTRACT: We explored the potential relevance of aqueous lysophosphatidic acid (LPA) and autotaxin (ATX) levels on postoperative outcomes of trabeculectomy, and the effects of ATX on fibrotic response in cultured human conjunctiva fibroblast (HCF) cells. We enrolled 70 glaucomatous eyes which underwent trabeculectomy, and quantified aqueous LPA and ATX. Those eyes were followed up for 12 months, and postoperative filtering blebs were evaluated using anterior segment optical coherence tomography. Also, the ATX-induced fibrotic changes in HCFs and the effects of an ATX inhibitor were assessed. Measured aqueous ATX and LPA levels were significantly different between glaucoma subtypes. In multivariate analyses, aqueous ATX levels were significantly correlated with the presence of needlings at 1, 3, 6 and 12 months after surgery. Exfoliative glaucoma, whose ATX level was significantly high, showed significantly increased numbers of needlings and a lower cumulative success rate without needlings. An in vitro study showed that fibrotic changes were upregulated by ATX treatment in HCFs, which was significantly suppressed by an ATX inhibitor. We presently demonstrate that aqueous ATX may be a prognostic factor affecting the fibrotic response in HCFs and bleb formation, and inhibition of ATX could be a therapeutic target after trabeculectomy.

SUBMITTER: Igarashi N

PROVIDER: S-EPMC6063955 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Role of the autotaxin-lysophosphatidic acid axis in glaucoma, aqueous humor drainage and fibrogenic activity.

Project description:Ocular hypertension due to impaired aqueous humor (AH) drainage through the trabecular meshwork (TM) is a major risk factor for glaucoma, a leading cause of irreversible blindness. However, the etiology of ocular hypertension remains unclear. Although autotaxin, a secreted lysophospholipase D and its catalytic product lysophosphatidic acid (LPA) have been shown to modulate AH drainage through TM, we do not have a complete understanding of their role and regulation in glaucoma patients, TM and AH outflow. This study reports a significant increase in the levels of autotaxin, lysophosphatidylcholine (LPC), LPA and connective tissue growth factor (CTGF) in the AH of Caucasian and African American open angle glaucoma patients relative to age-matched non-glaucoma patients. Treatment of human TM cells with dexamethasone, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) increased the levels of autotaxin protein, a response that was mitigated by inhibitors of glucocorticoid receptor, NF-kB and SMAD3. Dexamethasone, TNF-α, IL-1β and LPC treatment of TM cells also led to an increase in the levels of CTGF, fibronectin and collagen type 1 in an autotaxin dependent manner. Additionally, in perfused enucleated mouse eyes, autotaxin and LPC were noted to decrease, while inhibition of autotaxin was increased aqueous outflow through the TM. Taken together, these results provide additional evidence for dysregulation of the autotaxin-LPA axis in the AH of glaucoma patients, reveal molecular insights into the regulation of autotaxin expression in TM cells and the consequences of autotaxin inhibitors in suppressing the fibrogenic response and resistance to AH outflow through the TM.

| S-EPMC6863611 | biostudies-literature

Aqueous humor levels of TGF?2 and SFRP1 in different types of glaucoma.

Project description:BackgroundTo assess bioactive transforming growth factor-?2 (TGF?2) and secreted frizzled-related protein-1 (SFRP1) levels in aqueous humor (AH) of different types of glaucoma.MethodsAH samples were obtained immediately before ophthalmic surgery with a 27-gauge needle attached to a microsyringe from 126 eyes (105 patients) divided into five groups: cataract (control), primary open-angle glaucoma (POAG), chronic angle-closure glaucoma (CACG), primary angle-closure suspects (PACS), and acute angle-closure glaucoma (AACG). Bioactive TGF?2 and SFRP1 levels were assayed by ELISA.ResultsThe concentration of TGF?2 in AH of POAG patients, but not CACG, PACS, or AACG patients, was significantly higher than control eyes. However, within the AACG group, although the TGF?2 levels in AH did not differ significantly from the control level when all AACG patients were grouped together, there were differences when the AACG patients were divided into high and normal intraocular pressure (IOP); TGF?2 of AACG patients with high IOP (>?21?mmHg) was significantly higher than those with normal IOP. AH levels of SFRP1 were not significantly different among the groups. However, a statistical significant, negative correlation between SFRP1 and IOP existed in the POAG group. POAG patients with high IOP had lower levels of SFRP1 than those with normal IOP. In contrast, a significant, positive correlation between SFRP1 level and IOP was detected in the AACG group. AACG patients with high IOP had a higher level of SFRP1 than those with normal IOP. Concentrations of TGF?2 and SFRP1 did not correlate significantly with each other, or with age.ConclusionsThese results indicate that AH levels of TGF?2 and SFRP1 showed different profiles in different types of glaucomas.

| S-EPMC6683533 | biostudies-literature

MicroRNAs in the aqueous humor of patients with different types of glaucoma.

Project description:PurposeThe aim of the study was to compare the frequency and the level of expression of selected miRNAs in the aqueous humor of patients with various types of glaucoma.MethodsThe studied group consisted of 42 patients with glaucoma: 19 with primary open-angle glaucoma (POAG), 14 with pseudoexfoliation glaucoma (PEXG), 9 with primary angle closure glaucoma (PACG), and the control group of 36 patients with senile cataract without glaucoma. The real-time polymerase chain reaction method was used to analyze the expression of miRNAs.ResultsThere were no significant differences in the frequency and the level of miRNA expression between various types of glaucoma. There was a tendency for hsa-miR-6722-3p and hsa-miR-184 to be expressed more frequently in PEXG and hsa-miR-1260b in POAG. The expression levels of hsa-miR-1260b and hsa-miR-6515-3p were correlated with age in POAG. Target annotation and functional analyses showed that genes targeted by the most frequently expressed miRNAs (hsa-miR-1202, -1260b, -184, -187-5p, -6515-3p, -6722-3p, and hsa-mir-4634) are involved mainly in response to hypoxia, cardiovascular system development, and apoptosis.ConclusionHsa-miR-1260b was the most abundantly expressed among studied miRNAs and may be a potential biomarker of clinical status in PEXG and PACG.

| S-EPMC8352835 | biostudies-literature

Device-modified trabeculectomy for glaucoma.

Project description: Not available

| S-EPMC4715269 | biostudies-literature

Autotaxin-Lysophosphatidic Acid: From Inflammation to Cancer Development.

Project description:Lysophosphatidic acid (LPA) is a ubiquitous lysophospholipid and one of the main membrane-derived lipid signaling molecules. LPA acts as an autocrine/paracrine messenger through at least six G protein-coupled receptors (GPCRs), known as LPA1-6, to induce various cellular processes including wound healing, differentiation, proliferation, migration, and survival. LPA receptors and autotaxin (ATX), a secreted phosphodiesterase that produces this phospholipid, are overexpressed in many cancers and impact several features of the disease, including cancer-related inflammation, development, and progression. Many ongoing studies aim to understand ATX-LPA axis signaling in cancer and its potential as a therapeutic target. In this review, we discuss the evidence linking LPA signaling to cancer-related inflammation and its impact on cancer progression.

| S-EPMC5753009 | biostudies-other

Factors Predetermining Increased Aqueous Humour Flare in Long-Term Glaucoma Treatment.

Project description:Glaucoma patients often require long-term or even lifelong medical antiglaucomatous treatment. Benzalkonium chloride (BAK) is the most frequently used preservative in medical glaucoma treatment. Laser flare photometry is the noninvasive quantitative measurement of anterior chamber protein level and helps tracking intraocular inflammation. The purpose of our study was to evaluate the ocular aqueous humour flare in glaucoma patients, scheduled for cataract surgery without any other ocular diseases, and the association with pseudoexfoliation (PEX) syndrome, number of medications used, and BAK. A prospective case-control age- and gender-matched study, including open-angle glaucoma patients (>2 years of treatment) with cataract, matched with cataract patients with no other ocular pathology (control group). We found that the aqueous humour flare was higher in the glaucoma group than in the control group. PEX syndrome increased the aqueous humour flare independently from glaucoma diagnosis. The number of used antiglaucomatous medications correlated moderately with the aqueous humour flare. The BAK index showed weak positive correlation with aqueous humour flare. A variety of factors can affect aqueous humour flare increase, including PEX syndrome, medical substance used to treat glaucoma, number of different medications, and presence of BAK. The combination of these factors is of key importance to long-term glaucoma treatment.

| S-EPMC7125493 | biostudies-literature

The Effects of Trabeculectomy on Pseudoexfoliation Glaucoma and Primary Open-Angle Glaucoma.

Project description:Purpose:To compare long-term effects of trabeculectomy on pseudoexfoliation glaucoma (PXG) and primary open-angle glaucoma (POAG). Methods:This retrospective case-control study included 53 eyes of PXG and 76 eyes of POAG. Intraocular pressure (IOP), number of antiglaucoma medications used, surgical success rate, and occurrence of complications were observed and statistically analyzed in both groups at 3 and 6 months and at 1, 3, and 5 years after trabeculectomy. Surgical success was defined according to the following 3 criteria: (1) IOP???21?mmHg; (2) IOP???18?mmHg; (3) IOP???15?mmHg. Complete success is defined as patients met these criteria without medical treatment, and qualified success is defined as patients met these criteria with medical treatment (?3 medications). Cumulative probabilities of success were compared using the Kaplan-Meier survival analysis. Results:For the 3 criteria, there were no statistically significant differences in complete and qualified success rates between the two groups at 3 and 6 months after trabeculectomy (P > 0.05). For criterion A, complete success rates in PXG at 3 and 5 years after surgery were lower than those in POAG; for criterion B, complete and qualified success rates in PXG at 3 and 5 years after surgery were lower than those in POAG; for criterion C, complete and qualified success rates in PXG at 1, 3, and 5 years after surgery were lower than those in POAG, the differences were statistically significant (P < 0.05). Conclusions:The short-term success rates of both types of glaucoma were similar; however, the long-term success rate of PXG was significantly lower, and it was difficult to achieve long-term control of IOP at a low target level.

| S-EPMC7125473 | biostudies-literature

2-Carba-lysophosphatidic acid is a novel β-lysophosphatidic acid analogue with high potential for lysophosphatidic acid receptor activation and autotaxin inhibition.

Project description:Cyclic phosphatidic acid (cPA) is a naturally occurring phospholipid mediator that, along with its chemically stabilized analogue 2-carba-cyclic phosphatidic acid (2ccPA), induces various biological activities in vitro and in vivo. Although cPA is similar to lysophosphatidic acid (LPA) in structure and synthetic pathway, some of cPA biological functions apparently differ from those reported for LPA. We previously investigated the pharmacokinetic profile of 2ccPA, which was found to be rapidly degraded, especially in acidic conditions, yielding an unidentified compound. Thus, not only cPA but also its degradation compound may contribute to the biological activity of cPA, at least for 2ccPA. In this study, we determined the structure and examined the biological activities of 2-carba-lysophosphatidic acid (2carbaLPA) as a 2ccPA degradation compound, which is a type of β-LPA analogue. Similar to LPA and cPA, 2carbaLPA induced the phosphorylation of the extracellular signal-regulated kinase and showed potent agonism for all known LPA receptors (LPA1-6) in the transforming growth factor-α (TGFα) shedding assay, in particular for LPA3 and LPA4. 2carbaLPA inhibited the lysophospholipase D activity of autotaxin (ATX) in vitro similar to other cPA analogues, such as 2ccPA, 3-carba-cPA, and 3-carba-LPA (α-LPA analogue). Our study shows that 2carbaLPA is a novel β-LPA analogue with high potential for the activation of some LPA receptors and ATX inhibition.

| S-EPMC8405639 | biostudies-literature

An Autotaxin/Lysophosphatidic Acid/Interleukin-6 Amplification Loop Drives Scleroderma Fibrosis.

Project description:We previously implicated the lipid mediator lysophosphatidic acid (LPA) as having a role in dermal fibrosis in systemic sclerosis (SSc). The aim of this study was to identify the role of the LPA-producing enzyme autotaxin (ATX), and to connect the ATX/LPA and interleukin-6 (IL-6) pathways in SSc.We evaluated the effect of a novel ATX inhibitor, PAT-048, on fibrosis and IL-6 expression in the mouse model of bleomycin-induced dermal fibrosis. We used dermal fibroblasts from SSc patients and control subjects to evaluate LPA-induced expression of IL-6, and IL-6-induced expression of ATX. We next evaluated whether LPA-induced ATX expression is dependent on IL-6, and whether baseline IL-6 expression in fibroblasts from SSc patients is dependent on ATX. Finally, we compared ATX and IL-6 expression in the skin of patients with SSc and healthy control subjects.PAT-048 markedly attenuated bleomycin-induced dermal fibrosis when treatment was initiated before or after the development of fibrosis. LPA stimulated expression of IL-6 in human dermal fibroblasts, and IL-6 stimulated fibroblast expression of ATX, connecting the ATX/LPA and IL-6 pathways in an amplification loop. IL-6 knockdown abrogated LPA-induced ATX expression in fibroblasts, and ATX inhibition attenuated IL-6 expression in fibroblasts and the skin of bleomycin-challenged mice. Expression of both ATX and IL-6 was increased in SSc skin, and LPA-induced IL-6 levels and IL-6-induced ATX levels were increased in fibroblasts from SSc patients compared with controls.ATX is required for the development and maintenance of dermal fibrosis in a mouse model of bleomycin-induced SSc and enables 2 major mediators of SSc fibrogenesis, LPA and IL-6, to amplify the production of each other. Our results suggest that concurrent inhibition of these 2 pathways may be an effective therapeutic strategy for dermal fibrosis in SSc.

| S-EPMC5125861 | biostudies-literature

Steroid binding to Autotaxin links bile salts and lysophosphatidic acid signalling.

Project description:Autotaxin (ATX) generates the lipid mediator lysophosphatidic acid (LPA). ATX-LPA signalling is involved in multiple biological and pathophysiological processes, including vasculogenesis, fibrosis, cholestatic pruritus and tumour progression. ATX has a tripartite active site, combining a hydrophilic groove, a hydrophobic lipid-binding pocket and a tunnel of unclear function. We present crystal structures of rat ATX bound to 7?-hydroxycholesterol and the bile salt tauroursodeoxycholate (TUDCA), showing how the tunnel selectively binds steroids. A structure of ATX simultaneously harbouring TUDCA in the tunnel and LPA in the pocket, together with kinetic analysis, reveals that bile salts act as partial non-competitive inhibitors of ATX, thereby attenuating LPA receptor activation. This unexpected interplay between ATX-LPA signalling and select steroids, notably natural bile salts, provides a molecular basis for the emerging association of ATX with disorders associated with increased circulating levels of bile salts. Furthermore, our findings suggest potential clinical implications in the use of steroid drugs.

| S-EPMC4834639 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data