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Pedro Gonzalez, David L. Epstein, Teresa Borrás; Genes Upregulated in the Human Trabecular Meshwork in Response to Elevated Intraocular Pressure. Invest. Ophthalmol. Vis. Sci. 2000;41(2):352-361.
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purpose. To identify genes upregulated in perfused, intact human trabecular
meshwork (TM) in response to elevated intraocular pressure (IOP).
methods. Two pairs of anterior segments of normal human eyes from postmortem
donors were placed in culture and perfused 24 hours at constant flow (3μ
l/min). After reaching baseline, the flow of one eye from each pair
was raised to obtain an incremental pressure (ΔP) of 50 mm Hg for 6
hours. The anterior segments were then quickly frozen in liquid
nitrogen, and their TMs were dissected for RNA extraction. SMART cDNA
libraries were generated from control and high-pressure human TM RNAs
and hybridized to sets of identical high-density cDNA gene arrays.
These arrays contained 18,376 human expressed sequence tags (ESTs),
corresponding to both characterized and unknown genes. Differentially
expressed genes were identified by different-intensity hybridization
signals and confirmed by semi-quantitative polymerase chain reaction.
results. Eleven genes were found to be consistently upregulated in the human TM
by elevated IOP: interleukin-6, preprotachykinin-1, secretogranin-II,
cathepsin-L, stromelysin-1, thymosin-β4, α-tubulin,α
B-crystallin, glyceraldehyde-3-phosphate dehydrogenase,
metallothionein and Cu/Zn superoxide dismutase. The products of these
genes are involved in vascular permeability, secretion, extracellular
matrix remodeling, cytoskeleton reorganization, and reactive oxygen
conclusions. Elevated IOP induced specific upregulation of 11 physiologically
relevant genes. On the basis of their known activities, the products of
each of these genes might predict homeostatic mechanisms similar to
those involved in the regulation of blood vessel permeability. We
hypothesize that similar mechanisms might be involved in regulating
flow through Schlemm’s Canal endothelium.
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