Disease proteomics reveals altered basic gene expression regulation in leukocytes of Normal-Tension and Primary...

Glaucomatous damage is a neurodegenerative eye disease and one of the leading causes of blindness with 67 million patients worldwide. Major currently challenging questions include early diagnosis, risk evaluation, and follow-up. Circulating leukocytes have been demonstrated as potentially important source of disease specific markers. The relevance of expression alterations in leukocytes for glaucomatous damage needs to be clarified. Noteworthy, gene expression patterns of trabecular meshwork and Schlemm's canal, which are anatomically and functionally highly relevant for glaucoma pathology, were shown to be similar to those of circulating leukocytes. Here, we report extensive alterations in characteristic protein expression patterns of circulating leukocytes for Normal-Tension and Primary Open-Angle Glaucoma, as revealed by analysis of 2-D PAGE images. Among most conservative alterations we found the protein spot identified by MALDI-TOF as basic transcription factor activating protein-2beta (AP-2β). Western-blot analysis demonstrated significantly increased protein expression rates of AP-2β in both Normal-Tension and Primary Open-Angle Glaucoma versus controls. AP proteins are essential factors of the basic transcription regulation; AP-2 proteins play a decisive role, particularly, in morphogenesis of eye. Conservative AP-2 up-regulation is of special importance in terms of basic transcriptional dysregulation that might be specific for glaucoma disease.