51 research outputs found
Glaucoma-on-a-chip:An in vitro model for glaucoma drug discovery based on mimicking the mechanical stress of high eye pressure
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
Sex differences in the association of prediabetes and type 2 diabetes with microvascular complications and function: the Maastricht Study
Background Women with type 2 diabetes are disproportionally affected by macrovascular complications; we here investigated whether this is also the case for microvascular complications and retinal microvascular measures. Methods In a population-based cohort study of individuals aged 40-75 years (n = 3410; 49% women, 29% type 2 diabetes (oversampled by design)), we estimated sex-specific associations, and differences therein, of (pre)diabetes (reference: normal glucose metabolism), and of continuous measures of glycemia with microvascular complications and retinal measures (nephropathy, sensory neuropathy, and retinal arteriolar and venular diameters and dilatation). Sex differences were analyzed using regression models with interaction terms (i.e. sex-by- (pre)diabetes and sex-by-glycemia) and were adjusted for potential confounders. Results Men with type 2 diabetes (but not those with prediabetes) compared to men with normal glucose metabolism, (and men with higher levels of glycemia), had significantly higher prevalences of nephropathy (odds ratio: 1.58 95% CI (1.01;2.46)) and sensory neuropathy (odds ratio: 2.46 (1.67;3.63)), larger retinal arteriolar diameters (difference: 4.29 mu m (1.22;7.36)) and less retinal arteriolar dilatation (difference: - 0.74% (- 1.22; - 0.25)). In women, these associations were numerically in the same direction, but generally not statistically significant (odds ratios: 1.71 (0.90;3.25) and 1.22 (0.75;1.98); differences: 0.29 mu m (- 3.50;4.07) and: - 0.52% (- 1.11;0.08), respectively). Interaction analyses revealed no consistent pattern of sex differences in the associations of either prediabetes or type 2 diabetes or glycemia with microvascular complications or retinal measures. The prevalence of advanced-stage complications was too low for evaluation. Conclusions Our findings show that women with type 2 diabetes are not disproportionately affected by early microvascular complications.Prevention, Population and Disease management (PrePoD)Public Health and primary car
Argon laser trabeculoplasty: a retrospective and prospective study
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mmubn000001_068800878.pdf (publisher's version ) (Open Access)Promotor : A. Deutman319 p
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