glaucoma primary open angle glaucoma
Conditions
Interventions
None listed
Sponsors
Medisch Universitair Ziekenhuis Maastricht
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: The source population is the population of the participants of the Eye Tissue Bank Maastricht (ETBM). The ETBM is open for all glaucoma and cataract patients of the University Eye Clinic Maastricht to participate. In general, this is an elderly (glaucoma and cataract), Caucasian population inhabiting the south of Limburg. From the population of the ETBM, we previously selected the 175 participants of the blood biomarker study: POAG patients and controls. From these 175 participants of the blood biomarker study, we now select 3 study groups for the current study. 4.2 Inclusion criteria The blood biomarker study included 175 participants, POAG and Control from the ETBM with the following criteria: Inclusion criteria of the biomarker study: - POAG group: Well-documented diagnosis of POAG. - Control group: Well-documented ophthalmic history without glaucoma. - Over 18 years old Additional inclusion criteria of the current METC research proposal: - Group 1: POAG patients with lowest values of mtDNA copy number in blood cell DNA - Group 2: POAG patients, randomly selected - Group 3: Control patients, randomly selected; without glaucoma. We aim to collect fibroblast cell lines from 15 individuals per group. We expect to need skin biopsies from 15 to max 18 persons per group to achieve this. We will try to select these from the participants of the previous blood biomarker study. However, it will not be possible to include sufficient participants (15 to max 18) from the control group of the blood biomarker study to reach the required number of 15 individual fibroblast cell lines for the control group of the current study. To complete the required number for this group we will include additional control participants who we select directly (and randomly) from the source population (Eye Tissue Bank Maastricht), applying all appropriate inclusion and exclusion criteria of this control group and applying the age range which is present in the other (POAG) study groups of the current study.
Exclusion criteria
Exclusion criteria: Exclusion criteria of the blood biomarker study: - Systemic diseases in which mitochondria may be involved. - Use of drugs that affect mitochondrial function. Additional exclusion criteria of the current METC research proposal: - No informed consent - Use of oral anti-coagulants - Significant concurrent disease e.g., cancer, diabetes, neurological disorders (except for glaucomatous disorders), heart-related disorders, blood/platelet disorders or other diseases affecting the liver, kidney (except kidney stones) or the lungs (except bronchitis). - inherited metabolic disorder will be used as exclusion criterium for group 1 and 3, and as variable for group 2 - Other concurrent eye diseases e.g., uveitis, age-related macular degeneration or diabetic retinopathy. - Ongoing participation in other clinical trials that contain an intervention. - Any other factor that in the opinion of the investigator excludes the patient from the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Mitochondrial DNA copy number and mitochondrial function measured in in vitro assays of skin fibroblasts, compared between control (group 1) and POAG with low blood mtDNA copy number (group 2). Correlation between mitochondrial DNA copy number in the blood and mitochondrial function measured in fibroblasts within the POAG group (group 3). | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Effects of drugs on mitochondrial function as determined in fibroblast assays. In case that we can identify POAG patients with lower mitochondrial function than controls in a fibroblast assay, we will use this in vitro assay to test whether mitochondrial enforcing drugs can improve mitochondrial function in these fibroblasts assays. Dose-response curves will be established. 2. Explore the potential value of (additional) blood biomarkers for identifying POAG patients with mitochondrial dysfunction. After we have measured mitochondrial dysfunction with the gold standard method of functional assays in fibroblasts, we can use these data to document the relation between blood (or blood cell) biomarkers and the status of mitochondrial function. Besides the blood cell mtDNA copy number which has been determined before, these biomarkers include blood metabolomics analysis of metabolites of mitochondrial function (e.g. nicotinamide) and mitochondrial outer membrane potential measurement in peripheral blood mononuclear cells (PBMCs) as measured by TMRM staining. To assess the value of these blood biomarkers, we will calculate the relationship between the blood biomarker with the mitochondrial parameters measured in the fibroblast assays. 3. Further characterization of mitochondrial function. To reveal additional differences between POAG and control subjects, additional functional assays of mitochondrial function can be performed with the fibroblasts (e.g. Seahorse XF analysis). 4. Characterization of genetic variants DNA sequencing will be performed to study the possible association of genetic variants with mitochondtrial dysfunction and with POAG. | — |
Countries
Netherlands
Outcome results
None listed