30 research outputs found
Understanding the clinical and molecular basis of thyroid orbitopathy:a review of recent evidence
Thyroid eye disease (TED) is an autoimmune orbital inflammatory disease which ranges from mild to severe. Tissue remodeling, fibrosis and fat proliferation cause changes in the orbital tissues which can affect esthetics and visual function. In its severe form, it is sight threatening, debilitating, and disfiguring and may lead to social stigma, the embarrassment about which has an impact on the quality of life of those affected and the family members. The pathogenesis of TED, which is influenced by genetic, immunological, and environmental factors, is complex and not fully elucidated. However, it remains unknown what factors determine the severity of the disease. Recent research has revealed a number of diagnostic and prognostic biomarkers of this disease. In this overview of TED, we focus on new insights and perspectives regarding biological agents that may provide a basis for new treatment modalities.</p
Mapping mRNA Expression of Glaucoma Genes in the Healthy Mouse Eye
Purpose/Aim: Many genes have been associated with primary open-angle glaucoma (POAG). Knowing
exactly where they are expressed in the eye helps to unravel POAG pathology and to select optimal
targets for intervention. We investigated whether RNA in situ hybridization (RNA-ISH) is a convenient
technique to obtain detailed pan-ocular expression data of these genes. We tested this for four diverse
candidate POAG genes, selected because of unclear ocular distribution (F5 and Dusp1) and relevance for
potential new therapies (Tnf, Tgfβr3). Optn, a POAG gene with well-known ocular expression pattern
served as control.
Methods: We made a list of candidate glaucoma genes reported in genetic studies. A table of their
ocular expression at the tissue level was compiled using publicly available microarray data (the ocular
tissue database). To add cellular detail we performed RNA-ISH for Optn, Tnf, Tgfβr3, F5, and Dusp1 on
eyes of healthy, 2-month-old, pigmented, and albino mice.
Results: Expression of the Optn control matched with published immunohistochemistry data. Ocular
expression of Tnf was generally low, with patches of higher Tnf expression, superficially in the corneal
epithelium. F5 had a restricted expression pattern with high expression in the nonpigmented ciliary
body epithelium and moderate expression in the peripapillary region. Tgfβr3 and Dusp1 showed
ubiquitous expression.
Conclusions: RNA-ISH is a suitable technique to determine the ocular expression pattern of POAG
genes, adding meaningful cellular detail to existing microarray expression data. For instance, the high
expression of F5 in the nonpigmented ciliary body epithelium suggests a role of this gene in aqueous
humor dynamics and intraocular pressure. In addition, the ubiquitous expression of Tgfβr3 has implications for designing TGF-β-related glaucoma therapies, with respect to side effects. Creating pan-ocular
expression maps of POAG genes with RNA-ISH will help to identify POAG pathways in speci
Aqueous humor proteome of primary open angle glaucoma: A combined dataset of mass spectrometry studies
Analysis of the proteins of the aqueous humor can help to
elucidate the complex pathogenesis of primary open angle
glaucoma. Thanks to advances in liquid chromatography tandem mass spectrometry (LC-MS/MS) it is now possible to
identify hundreds of proteins in individual aqueous humor
samples without the need to pool samples. We performed
a systematic literature search to find publications that performed LC-MS/MS on aqueous humor samples of glaucoma
patients and of non-glaucomatous controls. Of the seven
publications that we found, we obtained the raw data of
three publications. These three studies used glaucoma patients that were clinically similar (i.e. undergoing glaucoma
filtration surgery) which prompted us to reanalyse and combine their data. Raw data of each study were analysed separately with the latest version of MaxQuant (version v1.6.11.0).
Outcome files were exported to Microsoft Excel. Samples belonging to the same patient were averaged to obtain peptide
expression values per individual. We compared the overlap of identified proteins using the VLOOKUP function of Excel
and a publicly available Venn diagram software. For the peptide sequences that can belong to multiple proteins (usually
of the same protein family), we initially included all possibly identified proteins. This ensured that we would not miss
a potential overlap between the studies due to differences in
identified peptide counts. Next, of those peptides of which
we compared multiple proteins, only one unique protein was
included in our analysis i.e. either the protein overlapping
bet
XEN® Gel Stent compared to PRESERFLO™ MicroShunt implantation for primary open-angle glaucoma: two-year results
Purpose: To evaluate the long-term efficacy and safety of two minimally invasive glaucoma surgery implants with a subconjunctival drainage approach: the XEN45 Gel Stent® (Xen) implant and the PRESERFLO™ MicroShunt (MicroShunt). Methods: Retrospective comparative case series of primary open-angle glaucoma (POAG) patients with at least 6 months of follow-up after a MicroShunt or Xen implantation augmented with mitomycin C. Results: Forty-one eyes of 31 patients underwent Xen implantation, and 41 eyes of 33 patients, MicroShunt implantation. Baseline characteristics were similar, except for more combined surgeries with phacoemulsification in the Xen group (37% vs. 2%). Mean baseline IOP ± standard deviation dropped from 19.2 ± 4.4 to 13.8 ± 3.8 mmHg (n = 26) in the Xen group and from 20.1 ± 5.0 to 12.1 ± 3.5 (n = 14) in the MicroShunt group at 24 months of follow-up (p = 0.19, t-test). The number of IOP-lowering medications dropped from 2.5 ± 1.4 to 0.9 ± 1.2 in the Xen group and from 2.3 ± 1.5 to 0.7 ± 1.1 in the MicroShunt group. The probability of qualified success was 73% and 79% at 24 months of follow-up for the Xen and MicroShunt groups, respectively. Postoperative complications were usually mild and self-limiting. The number of bleb needling and secondary glaucoma surgery procedures was similar in both groups; however, in the Xen group more additional MicroPulse® transscleral cyclophotocoagulation procedures were performed. Conclusion: Xen Gel Stent and PreserFlo MicroShunt implantations achieved comparable results in POAG eyes in terms of IOP-lowering and surgical success, with a similar high safety profile
The aqueous humor proteome of primary open angle glaucoma: An extensive review
Background: We reviewed the literature on the aqueous humor (AH) proteome of primary open angle glaucoma (POAG) patients in order to obtain deeper insight into the pathophysiology of POAG. Methods: We searched Pubmed and Embase up to May 2019 for studies that compared AH protein composition between POAG (cases) and cataract (controls). Untargeted studies (measuring the whole proteome, by LC-MS/MS) were divided into two subgroups depending on the type of surgery during which POAG AH was collected: glaucoma filtration surgery (subgroup 1) or cataract surgery (subgroup 2). We reanalyzed the raw data (subgroup 1) or combined the reported data (subgroup 2) to perform GO enrichment (GOrilla) and pathway analysis (Pathvisio). Results: Out of 93 eligible proteomic studies, seven were untargeted studies that identified 863 AH proteins. We observed 73 differentially expressed proteins in subgroup 1 and 87 differentially expressed proteins in subgroup 2. Both subgroups were characterized by activation of the acute immune response, dysregulation of folate metabolism and dysregulation of the selenium micronutrient network. For subgroup 1 but not for subgroup 2, proteins of the complement system were significantly enriched. Conclusion: AH proteome of POAG patients shows strong activation of the immune system. In addition, analysis suggests dysregulation of folate metabolism and dysregulation of selenium as underlying contributors. In view of their glaucoma surgery, POAG patients of subgroup 1 most likely are progressive whereas POAG patients in subgroup 2 most likely have stable POAG. The proteome difference between these subgroups suggests that the complement system plays a role in POAG progression
Modeling the Mechanical Parameters of Glaucoma
Glaucoma is a major eye disease characterized by a progressive loss of retinal ganglion cells (RGCs). Biomechanical forces as a result of hydrostatic pressure and strain play a role in this disease. Decreasing intraocular pressure is the only available therapy so far, but is not always effective and does not prevent blindness in many cases. There is a need for drugs that protect RGCs from dying in glaucoma; to develop these, we need valid glaucoma and drug screening models. Since in vivo models are unsuitable for screening purposes, we focus on in vitro and ex vivo models in this review. Many groups have studied pressure and strain model systems to mimic glaucoma, to investigate the molecular and cellular events leading to mechanically induced RGC death. Therefore, the focus of this review is on the different mechanical model systems used to mimic the biomechanical forces in glaucoma. Most models use either cell or tissue strain, or fluid- or gas-controlled hydrostatic pressure application and apply it to the relevant cell types such as trabecular meshwork cells, optic nerve head astrocytes, and RGCs, but also to entire eyes. New model systems are warranted to study concepts and test experimental compounds for the development of new drugs to protect vision in glaucoma patients
Diabetic retinal neurodegeneration associated with synaptic proteins and functional defects: A systematic review
Diabetic retinopathy (DR) is the most common ophthalmological complication of diabetes mellitus (DM) and a leading cause of preventable visual impairment. In DM, retinal neurodegenerative changes precede microvascular changes which can be assessed by electrophysiological and advanced imaging techniques. Studies measuring retinal neurodegenerative changes in DM were systematically evaluated in this review. Included studies have assessed retinal neurodegeneration in diabetic rodents by combining clinically used diagnostic techniques and molecular assays. Significant impairment was noticed in electrophysiology data in the diabetic retina as compared to the non-diabetic retina. Also, a significant reduction in synaptic protein levels was noticed in the diabetic retina compared to the non-diabetic retina. Even though retinal neurodegeneration was noticed, no vascular abnormalities were seen in the diabetic retina. However, little is known about molecular mechanisms behind diabetic retinal neurodegeneration (DRN), which explains the need for further investigation to detect DR in the early stages of diabetes
Prediction of Glaucomatous Visual Field Progression Using Baseline Clinical Data
Purpose: To develop a prediction model for glaucomatous visual field progression using easily accessible baseline clinical data. Patients and Methods: We collected baseline data of 613 consecutive patients with open-angle glaucoma from 2001 to 2003. The rate of visual field progression was calculated using the Visual Field Index (VFI) of routine follow-up examinations until 2010. Baseline data of 333 patients from 3 hospitals were used to develop a model to predict the rate of VFI progression using a linear regression analysis and univariate preselection (P <0.1) of 8 candidate predictors. The performance of the model was investigated using R-2, the area under the receiver-operating characteristic curve, and calibration plots. The prediction model was internally validated using bootstrapping and externally validated in 280 patients from 2 other hospitals. Results: After a mean follow-up period of 5.8 years of all 613 eyes, the mean rate of VFI progression was -1.6% per year. The final model contained the following predictors: age, baseline intraocular pressure, and baseline visual field status. During model development, 10.3% of the observed variation in VFI rates was explained by the model. The area under the receiver-operating characteristic curve was 0.76 when the prediction model was used to detect a VFI rate of -3% per year or worse, which decreased to 0.71 at external validation. Conclusions: Although our prediction model could explain only a small amount of the variance in visual field progression, it may offer the possibility to identify subgroups of treated patients with high rates of visual field progression, thereby providing an opportunity to select those patients for more intensive treatment