Abstract
Purpose: :
The mechanical effect of raised intraocular pressure is a recognised stimulus for optic neuropathy in primary open angle glaucoma (POAG). The purpose of this study was to investigate the pattern of gene expression induced by altering the levels of mechanical stresses on both Lamina Cribrosa Cells from normal patients and patients diagnosed with primary open angle glaucoma (POAG).
Methods: :
Confluent LC cells were stretched using the Flexercell tension plus FX-4000T system (Flexercell International Corp.). Cells were serum starved for 24 hrs and stretched at 3% equating to normal IOP for 24 hours prior to 1s cycles (1Hz) of three separate stretch conditions, 3% (normal IOP), 15% (POAG IOP) and 25% (pathological IOP) conditions for a further 24 hrs. Cells in a static condition were also used for comparison purposes. A Low Density Array (LDA) was run to focus on ninety six genes. Gene ontology’s included ECM, cell proliferation, growth factor activity, and signal transduction.
Results: :
Significant changes in genes and proteins complicit in ECM matrix remodelling were expressed by LC cells under cyclical mechanical strain approximating POAG conditions. In the groups of genes that were looked at in the low density array variation was noticeable between the two cell types. Differences in expression of ECM genes included elastin, collagens, thrombospondin 1, perlecan, and lysl oxidase. These differences were seen in POAG cell and normal Lamina cribrosa depending on the degrees of stretch that the cells were subjected too.The LDA also demonstrated that the degree of expression of growth factors like TGF-2, BMP-7, VEGF and EGF depended on the degree of stretch the cells were subjected to.
Keywords: lamina cribrosa • gene/expression • stress response