Ocular Surface Changes in Prostaglandin Analogue-Treated Patients.
Ontology highlight
ABSTRACT:
SUBMITTER: Shen W
PROVIDER: S-EPMC6925925 | biostudies-literature | 2019
REPOSITORIES: biostudies-literature
Publications
Ocular Surface Changes in Prostaglandin Analogue-Treated Patients.
Shen Wencui W Huang Bingqing B Yang Jin J
Journal of ophthalmology 20191210
Glaucoma is the second leading cause of blindness globally. Reducing intraocular pressure (IOP) has been acknowledged to be the main therapy for glaucoma. Prostaglandin analogues (PGAs) have become the first-line therapy for patients with glaucoma due to their powerful efficacy for lowering (IOP). However, usage of PGAs can also cause several notable side effects, including the changes in ocular surface. The relationship between PGAs and ocular surface changes is complicated and still remains un ...[more]
Similar Datasets
Project description:BackgroundIn our earlier genome-wide association study on Stevens-Johnson Syndrome (SJS) and its severe variant, toxic epidermal necrolysis (TEN), we found that in Japanese patients with these severe ocular surface complications there was an association with prostaglandin E receptor 3 (EP3) gene (PTGER3) polymorphisms. We also reported that EP3 is dominantly expressed in the ocular surface-, especially the conjunctival epithelium, and suggested that EP3 in the conjunctival epithelium may down-regulate ocular surface inflammation. In the current study we investigated the expression of EP3 protein in the conjunctiva of patients with various ocular surface diseases such as SJS/TEN, chemical eye burns, Mooren's ulcers, and ocular cicatricial pemphigoid (OCP).Methodology/principal findingsConjunctival tissues were obtained from patients undergoing surgical reconstruction of the ocular surface due to SJS/TEN, chemical eye burns, and OCP, and from patients with Mooren's ulcers treated by resection of the inflammatory conjunctiva. The controls were nearly normal human conjunctival tissues acquired at surgery for conjunctivochalasis. We performed immunohistological analysis of the EP3 protein and evaluated the immunohistological staining of EP3 protein in the conjunctival epithelium of patients with ocular surface diseases. EP3 was expressed in the conjunctival epithelium of patients with chemical eye burns and Mooren's ulcer and in normal human conjunctival epithelium. However, it was markedly down-regulated in the conjunctival epithelium of SJS/TEN and OCP patients.ConclusionsWe posit an association between the down-regulation of EP3 in conjunctival epithelium and the pathogenesis and pathology of SJS/TEN and OCP, and suggest a common mechanism(s) in the pathology of these diseases. The examination of EP3 protein expression in conjunctival epithelium may aid in the differential diagnosis of various ocular surface diseases.
| S-EPMC3178633 | biostudies-literature
Project description:ObjectivesTo confirm the downregulation of PTGER4 mRNA in the conjunctiva of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and ocular cicatricial pemphigoid (OCP) patients and to examine the expression of its EP4 protein in the conjunctival epithelium of patients with various ocular surface disorders.DesignCase-control study.Setting and participantsWe performed quantitative reverse transcription-PCR (RT-PCR) analysis of PTGER4 mRNA in conjunctival tissue sections from patients with SJS/TEN and OCP to confirm the downregulation of PTGER4 mRNA expression. We also analysed EP4 immunohistologically in other ocular surface disorders. Conjunctival tissues were obtained from patients undergoing surgical reconstruction of the ocular surface due to chemical eye burns, subacute SJS/TEN or chronic SJS/TEN, chronic OCP, severe graft versus host disease (GVHD) and from patients with Mooren's ulcers treated by resection of the inflammatory conjunctiva.Primary and secondary outcome measuresThe expression of PTGER4 mRNA and EP4 protein assessed by quantitative RT-PCR assay and immunohistological methods.ResultsPTGER4 mRNA was significantly lower in conjunctival tissues from SJS and OCP patients than in the control conjunctivochalasis samples. EP4 protein was detected in conjunctival epithelium from patients with chemical eye burn and in control conjunctival epithelium from patients with conjunctivochalasis. Its expression varied in conjunctival epithelium from patients with Mooren's ulcer. We did not detect EP4 immunoreactivity in conjunctival epithelium from patients with subacute SJS/TEN, severe GVHD, chronic SJS/TEN or OCP.ConclusionsThe strong downregulation of EP4 expression in conjunctival epithelium from patients with OCP or SJS/TEN may be attributable to ocular surface inflammation.
| S-EPMC3488701 | biostudies-literature
Project description:Statin-related muscle side effects are a constant healthcare problem since patient compliance is dependent on side effects. Statins reduce plasma cholesterol levels and can prevent secondary cardiovascular diseases. Although statin-induced muscle damage has been studied, preventive or curative therapies are yet to be reported. We exposed primary human muscle cell populations (n = 22) to a lipophilic (simvastatin) and a hydrophilic (rosuvastatin) statin and analyzed their expressome. Data and pathway analyses included GOrilla, Reactome and DAVID. We measured mevalonate intracellularly and analyzed eicosanoid profiles secreted by human muscle cells. Functional assays included proliferation and differentiation quantification. More than 1800 transcripts and 900 proteins were differentially expressed after exposure to statins. Simvastatin had a stronger effect on the expressome than rosuvastatin, but both statins influenced cholesterol biosynthesis, fatty acid metabolism, eicosanoid synthesis, proliferation, and differentiation of human muscle cells. Cultured human muscle cells secreted ω-3 and ω-6 derived eicosanoids and prostaglandins. The ω-6 derived metabolites were found at higher levels secreted from simvastatin-treated primary human muscle cells. Eicosanoids rescued muscle cell differentiation. Our data suggest a new aspect on the role of skeletal muscle in cholesterol metabolism. For clinical practice, the addition of omega-n fatty acids might be suitable to prevent or treat statin-myopathy.
| S-EPMC7005895 | biostudies-literature
Project description:PurposeOcular surface microbiome changes can affect meibomian gland dysfunction (MGD) development. This study aimed to delineate differences among the microbiome of eyelid skin, conjunctiva, and meibum in healthy controls (HCs) and patients afflicted with MGD.MethodsShotgun metagenomic analysis was used to determine if there are differences between the microbial communities in ocular sites surrounding the meibomian gland in healthy individuals and patients afflicted with MGD.ResultsThe meibum bacterial content of these microbiomes was dissimilar in these two different types of individuals. Almost all of the most significant taxonomic changes in the meibum microbiome of individuals with MGD were also present in their eyelid skin, but not in the conjunctiva. Such site-specific microbe pattern changes accompany increases in the gene expression levels controlling carbohydrate and lipid metabolism. Most of the microbiomes in patients with MGD possess a microbe population capable of metabolizing benzoate. Pathogens known to underlie ocular infection were evident in these individuals. MGD meibum contained an abundance of Campylobacter coli, Campylobacter jejuni, and Enterococcus faecium pathogens, which were almost absent from HCs. Functional annotation indicated that in the microbiomes of MGD meibum their capability to undergo chemotaxis, display immune evasive virulence, and mediate type IV secretion was different than that in the microbiomes of meibum isolated from HCs.ConclusionsMGD meibum contains distinct microbiota whose immune evasive virulence is much stronger than that in the HCs. Profiling differences between the meibum microbiome makeup in HCs and patients with MGD characterizes changes of microbial communities associated with the disease status.
| S-EPMC7425691 | biostudies-literature
Project description:PurposeThere is growing evidence for a critical role of the microbiome in ocular health and disease. We performed a prospective, observational study to characterize the ocular surface microbiome (OSM) in four chronic ocular surface diseases (OSDs) and healthy controls.MethodsSterile swabs were used to collect samples from each eye of 39 patients (78 eyes). Sterile technique and multiple controls were used to assess contamination during DNA extraction, amplification and sequencing. Concurrent use of topical antibiotics, steroids, and bandage contact lenses (BCLs) was documented.ResultsDespite the low biomass of the ocular surface, 47/78 (60%) eyes sampled had positive sequencing reads. We observed that half of patients (8/17, 47%) had distinct microbiomes in each eye. Healthy controls had a Lactobacillus/Streptococcus mixture or significant Corynebacterium. Staphylococcus predominated in 4/7 (57%) patients with Stevens-Johnson Syndrome (SJS) in at least one eye, compared to 0/10 healthy controls. Interestingly, 8/11 (73%) eyes with SJS were using BCLs, including 4/5 (80%) eyes dominated by Staphylococcus. Lax eyelid syndrome (LES) and Dry Eye Disease (DED) patients had similar OSMs, with Corynebacterium being the most prevalent bacteria. Alpha diversity was higher in controls and ocular graft-vs-host (oGVHD) patients compared to the other OSDs.ConclusionsOnly 50% of the 39 patients had similar microbiomes in each eye. A majority of healthy eyes had a Lactobacillus/Streptococcus mix or Corynebacterium microbiome. Staphylococcus predominated in SJS, Lactobacillus in oGVHD, and Corynebacterium in DED and LES. There may be an association between different OSDs and the microbiome.
| S-EPMC7905829 | biostudies-literature
Project description:PurposeTo report the outcomes of prosthetic replacement of the ocular surface ecosystem (PROSE) treatment in pediatric patients with chronic ocular surface disease associated with Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN).DesignRetrospective, interventional case series.MethodsPatients aged 18 years or younger seen in consultation for PROSE treatment at a single center between January 1992 and December 2016 with a history of SJS/TEN were reviewed. Demographics, etiology of SJS/TEN, age at treatment milestones, best-corrected visual acuity (BCVA) at treatment milestones, and treatment failures were recorded. BCVA at the initial presentation visit was compared to BCVA at the time of PROSE device dispense and at the last recorded visit.ResultsTwenty-seven female and 22 male patients were reviewed. Reported etiology was antibiotic (n = 19), antiepileptic (n = 9), antipyretic (n = 9), other (n = 3), and unknown (n = 9). The mean age was 6.4 years at disease onset and 9.3 years at time of initial presentation. The mean duration of follow-up was 5.45 years. The median BCVA at the initial presentation was 0.6 logMAR (20/80 Snellen), and was significantly improved to 0.18 logMAR (20/30 Snellen) at the time a PROSE device was dispensed (P < .0001). The median BCVA at the last recorded visit was significantly improved to 0.18 logMAR (20/30 Snellen, P = .0004). There were 15 patients who failed PROSE treatment (30.6%).ConclusionsPROSE treatment is feasible in over two thirds of pediatric patients with chronic ocular surface disease related to SJS/TEN and results in significant improvement in vision that is durable over a period of many years.
| S-EPMC6532769 | biostudies-literature
Project description:Inflammation of the cornea is known as keratitis, and bacteria, fungi, protozoans, and viruses are the etiological agents of this disease. Delayed treatment of keratitis could result in loss of vision and, under certain severity conditions, the removal of an eye and its associated structures. In the current study, the ocular surface (conjunctiva and cornea) mycobiomes of individuals with bacterial keratitis were compared with the ocular mycobiome (conjunctiva) of healthy individuals, free of any ocular morbidity. Mycobiomes were generated through NGS approach using conjunctival swabs and corneal scrapings as the source of DNA from which ITS2 was amplified and sequenced, as a proxy to identify fungi. The results indicated significant changes in the alpha-diversity indices and in the abundance at the phylum and genera level. Hierarchical clustering using a heatmap showed that the mycobiomes were different. Furthermore, NMDS plots also differentiated the mycobiomes in the three cohorts, implying dysbiosis in the mycobiomes of the conjunctivae and corneal scrapings of bacterial keratitis individuals compared to control individuals. A preponderance of negative interactions in the hub genera in the conjunctival swabs of bacterial keratitis individuals compared to healthy controls further re-emphasized the differences in the mycobiomes. The dysbiotic changes at the genera level in conjunctivae and corneal scrapings of bacterial keratitis individuals are discussed with respect to their possible role in causing or exacerbating ocular surface inflammation. These results demonstrate dysbiosis in the ocular mycobiome in bacterial keratitis patients compared to healthy controls for the first time.
| S-EPMC11182091 | biostudies-literature
Project description:Dry eye disease can be a consequence of lacrimal gland insufficiency in Sjögren's Syndrome or increased tear film evaporation despite normal lacrimal gland function. To determine if there is a correlation between severity effects in these models and underlying pathophysiological responses, we compared the time dependent changes in each of these parameters that occur during a 6 week period. Dry eye was induced in 6-week-old female C57BL/6 mice by exposing them to an Intelligently Controlled Environmental System (ICES). Sixty mice were housed in ICES for 1, 2, 4 and 6 weeks respectively. Twelve were raised in normal environment and received subcutaneous injections of scopolamine hydrobromide (SCOP) 3 times daily for 5 days. Another sixty mice were housed in a normal environment and received no treatment. Corneal fluorescein staining along with corneal MMP-9 and caspase-3 level measurements were performed in parallel with the TUNEL assay. Interleukin-17(IL-17), IL-23, IL-6, IL-1, TNF-α, IFN-γ and TGF-β2 levels were estimated by real-time PCR measurements of conjunctival and lacrimal gland samples (LGs). Immunohistochemistry of excised LGs along with flow cytometry in cervical lymph nodes evaluated immune cell infiltration. Light and transmission electron microscopy studies evaluated LGs cytoarchitectural changes. ICES induced corneal epithelial destruction and apoptosis peaked at 2 weeks and kept stable in the following 4 weeks. In the ICES group, lacrimal gland proinflammatory cytokine level increases were much lower than those in the SCOP group. In accord with the lower proinflammatory cytokine levels, in the ICES group, lacrimal gland cytosolic vesicular density and size exceeded that in the SCOP group. ICES and SCOP induced murine dry eye effects became progressively more severe over a two week period. Subsequently, the disease process stabilized for the next four weeks. ICES induced local effects in the ocular surface, but failed to elicit lacrimal gland inflammation and cytoarchitectural changes, which accounts for less dry eye severity in the ICES model than that in the SCOP model.
| S-EPMC4295848 | biostudies-literature
Project description:Ocular surface microbiome in dupilumab associated ocular surface disease
| PRJEB57775 | ENA
Project description:PurposeTo investigate the ocular surface (OS) commensal bacteria profiles of patients with diabetes mellitus (DM) and dry eye disease (DED).MethodsIn the present study, subjects were assigned to four groups: 37 to the diabetic mellitus with dry eye disease (DM with DED) group, 22 to the diabetes mellitus (DM)-only group, 34 to the dry eye disease (DED)-only group, and 22 to the control group. Tear fluid was collected using Schirmer's tear secretion test paper. 16S ribosomal ribonucleic acid (rRNA) gene sequencing was used to analyze the bacterial microbiota.ResultsThe DM with DED group showed the highest operational taxonomic unit (OTU) numbers and alpha diversity and the most different beta diversity. The groups shared the four most abundant phyla, accounting for over 96% of the total abundance. At the genus level, there were 10 types of overlap in the core microbiota in the groups. They showed significant differences between the groups. Additionally, the DM with DED group and the control group showed four unique core genera, respectively. Unclassified Clostridiales and Lactobacillus were the core microbiota members of the DM with DED group, the DM-only group, and the DED-only group, but not the control group.ConclusionsIn the present study, our results showed that the patients in the DM with DED group had a more complex and comprehensive ocular surface microbial composition. To the best of our knowledge, this is the first study to reveal the microbial profile of dry eye disease in patients with diabetes mellitus.
| S-EPMC8444464 | biostudies-literature