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Markus Kuehn; Expression of ER Stress Markers in the Human Trabecular Meshwork. Invest. Ophthalmol. Vis. Sci. 2013;54(15):374.
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Dysfunction and loss of the cells residing within the trabecular meshwork (TM) likely contributes to the development of elevated intraocular pressure (IOP) in glaucoma. Endoplasmic reticulum (ER) stress in TM cells may result from a variety of environmental and genetic factors and can result in cell death. This study was designed to evaluate if ER stress does occur in TM cells of older patients and whether it occurs more frequently in eyes derived from primary open angle glaucoma (POAG) patients than in age-matched controls.
We conducted an immunohistochemical study using 30 human donor eyes with primary open angle glaucoma and age-matched controls. Human donor eyes were obtained from the local eye bank and preserved in 4% paraformaldehyde within 8 hrs postmortem. Sagittal sections of the anterior segment were incubated with antibodies directed against GADD153/CHOP, GRP78, and caspase 9. Labeling intensities in TM cells were scored independently by two investigators masked to the disease status of the individuals. Levels of these proteins were also determined using Western blots.
Our data demonstrate GADD153 and GRP78 can frequently be detected in the TM of older human eye donors. Moderate or strong immunoreactivity was found in the majority of both POAG eyes and those obtained from control donors. However, samples with the most pronounced immunoreactivity tended to be derived from POAG donors. Caspase-9 immunoreactivity was observed less frequently than that for GADD178 or GRP78 and also occurred in TM cells from both POAG and control donors.
Expression of markers of ER stress is a common feature in TM cell in the aged human eye. These include chaperones (GRP78) as well as pro-apoptotic molecules (Chop, caspase9). The TM of human eyes with POAG contains fewer TM cells suggesting that TM cells in these individuals may be less well equipped to survive sustained ER stress.
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