Cellular Proteome From Leukocytes of Glaucoma Patients in Comparison With Patients With Alzheimer's Disease

NCT ID: NCT00691340

Last Updated: 2015-03-10

Basic Information

• Recruitment Status: WITHDRAWN
• Study Classification: OBSERVATIONAL
• Study Start Date: 2008-06-30
• Study Completion Date: 2011-08-31

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.

Conditions

Alzheimer's Disease; Glaucoma

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: PROSPECTIVE

Study Groups

1

Control 1 (young subjects)

No interventions assigned to this group

2

Control 2 (old subjects)

No interventions assigned to this group

3

Glaucoma patients

No interventions assigned to this group

4

Alzheimer patients

No interventions assigned to this group

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University Hospital, Bonn

OTHER

Sponsor Role: collaborator

University Hospital, Basel, Switzerland

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Selim Orguel, MD

Role: STUDY_DIRECTOR

University Hospital, Basel, Switzerland

Other Identifiers

075-WUK-2008-002

Identifier Type: -

Identifier Source: org_study_id