Clinical trial NCT00691340: Cellular Proteome From Leukocytes of Glaucoma Patients in Comparison With Patients With Alzheimer's Disease
Official title: Systematic Characterization of the Cellular Proteome From Human Leukocytes of Glaucoma Patients in Comparison With Patients With Alzheimer's Disease
Study type: OBSERVATIONAL
Overall status: WITHDRAWN
Conditions: Alzheimer's Disease
Glaucoma
Keywords: POAG
Alzheimer's disease
cellular proteome
human leucocytes
vasospasm
Healthy subjects
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
Collaborators: name: University Hospital, Bonn
First posted: 2008-06-05
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Glaucoma patients Alzheimer's patients

Brief summary: Glaucoma is a worldwide leading cause of blindness. The key feature of this ocular neuropathy is characterized by an excavating optic nerve head. Loss of retinal ganglion cells is the final end point in blinding diseases of the optic nerve such as glaucoma. It is known that neuronal cell death in glaucoma occurs by an apoptotic mechanism. In earlier studies the investigators could demonstrate that the process of apoptosis is reflected in circulating leukocytes by different parameters, like differential mRNA expression and an increased fragmentation of the DNA. Such alterations point out a relationship between cellular stress and apoptotic events.

Based on the results of mRNA-expression the investigators also expect alterations on the protein level.

This study is, therefore, designed to characterize the proteome related to the proteins involved in cell death related pathways.

Thus, the expression pattern of several proteins in leukocytes from patients with primary open angle glaucoma will be analyzed by techniques like Western-blot and tandem mass spectrometry. These samples will be compared with samples from healthy controls. In addition, they will also be compared with samples from patients with Alzheimer's disease. Since glaucoma is a neurodegenerative disease, these patients will be included as positive controls in this study.

Detailed description: Hypothesis:

Differences in the proteome concerning cell death pathways of glaucoma patients correspond to the differences in the mRNA expression of these patients.

Specific aims:

Characterization of the cellular proteome from human leukocytes of glaucoma patients compared to healthy controls and patients with Alzheimer's disease.

Background:

Glaucoma is a worldwide leading cause of blindness. The key feature of this ocular neuropathy is characterized by an excavating optic nerve head. Loss of retinal ganglion cells is the final end point in blinding diseases of the optic nerve such as glaucoma. It is known that neuronal cell death in glaucoma occurs by an apoptotic mechanism. In earlier studies we could demonstrate that this cell death is reflected in circulating leukocytes by different parameters, like differential mRNA expression, and an increased fragmentation of the DNA. The differences in mRNA expression indicate a close relationship to cellular stress conditions and apoptotic events: increased mRNA expression was detected for p53, 20S proteasome alpha subunit, ABC1 transporter, p21(WAF1/CIP1), 14-3-3 sigma factor, MMP-9 and MMP-14, and TIMP-1.

Based on the assumption that glaucoma patients may differ on the level of their expression for these mRNAs, we expect that similar differences should exist at the protein level.

This study is, therefore, designed to characterize the proteome related to the proteins involved in cell death related pathways.

Eligibility criteria: Inclusion Criteria:

* German native speakers
* Age between 18-85 years
* Primary open-angle glaucoma (POAG) with and without vasospasm
* An inclusion criterion for one control group is Alzheimer's disease.

Exclusion Criteria:

Any history of:

* Ocular or systemic diseases other than glaucoma or Alzheimer's disease
* Drug or alcohol abuse
* Any condition potentially interfering with the visual field results. Visual fields will be obtained from the chart.
* Mental impairment interfering with the ability to cooperate and understand the purpose of this study.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: University Hospital, Basel, Switzerland
name: Selim Orguel, MD
role: STUDY_DIRECTOR
References: