Purchase this article with an account.
U.M. Schloetzer-Schrehardt, M. Zenkel, E. Poeschl, G.O. Naumann; Differential Gene Expression in Pseudoexfoliation Syndrome and Glaucoma . Invest. Ophthalmol. Vis. Sci. 2003;44(13):4236.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Purpose: To identify and characterize genes differentially expressed in anterior segment tissues of eyes with pseudoexfoliation (PEX) syndrome and glaucoma. Methods: Gene expression patterns of anterior segment tissues (iris, ciliary processes, lens capsules) obtained from 3 eyes with PEX syndrome/glaucoma and 3 age-matched control eyes were analyzed by repeated Subtractive Hybridization and Differential Screening (SSH) as well as by cDNA macroarrays (Atlas Human cDNA Expression Arrays, Clontech). Potential candidates of differentially expressed genes were tested by Northern Blot analysis, RT-PCR, and in situ-hybridization for differential expression and were finally sequenced and compared to sequence databases. Immunohistochemistry was used to demonstrate tissue-specific expression of selected gene products. Results: About 50 genes were identified to be differentially expressed in PEX tissues by SSH and about 100 by macroarray analysis; out of these, 30 genes could be confirmed and identified. Relevant genes found to be consistently upregulated included elastic microfibril components (LTBP-1/2), cross-linking enzymes (transglutaminase-2), enzyme inhibitors (TIMP-1/2), growth factors (TGF-ß1), proinflammatory cytokines (IL-1/2), stress proteins (HSPs, apolipoprotein D), dehydrocholesterolreductase, transcription factors (NfkappaB), and signal transduction molecules (AKAP-2). Downregulated genes comprised extracellular chaperones (clusterin), antioxidative factors (glutathion-S-transferases), matrix enzymes (elastase), cell adhesion molecules (ICAM-1), transcription factors (HLHP 1R21) and DNA repair proteins (hmhl1). Interestingly, the gene coding for adenosine A3 receptor, which is involved in the regulation of aqueous humor production and intraocular pressure, was overexpressed in the ciliary processes of eyes with PEX glaucoma by factor 20 to 35. Conclusions: These findings suggest that PEX syndrome represents a special type of stress-induced elastosis. Growth factors, a subtle inflammatory component, increased cellular and oxidative stress, extensive cross-linking processes, a proteolytic imbalance, and impaired DNA repair mechanisms appear to be causally involved in this fibrotic process. In this scenario, TGF-ß1 and TIMP-1/2 may be key molecules, which could serve as prognostic parameters and therapeutic targets. Additionally, the adenosine A3 receptor subtype may be involved in glaucoma development in PEX patients.
This PDF is available to Subscribers Only