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.
