High ER stress may contribute to POAG

Seattle-Primary open-angle glaucoma (POAG) is generally associated with elevations in IOP, and damage to the cells residing within the trabecular meshwork is most likely a contributing factor, said Markus H. Kuehn, PhD.

But the trabecular meshwork in human eyes with POAG has fewer cells, which suggests that they may be more poorly equipped to survive sustained endoplasmic reticulum (ER) stress.

“Endoplasmic reticulum stress markers are commonly present in trabecular meshwork cells of older people,” said Dr. Kuehn, associate professor of ophthalmology and visual sciences at the University of Iowa, Iowa City. “These include GRP78 as well as the pro-apoptotic molecules Chop and caspase-9. Expression levels vary considerably between individuals.”

Damage to the trabecular meshwork can result from a number of factors, and morphologic changes include increased stiffening of the tissue, loss of cells with activation of the remaining cells, and cytoskeletal reorganization. ER stress in the meshwork cells can occur from a variety of environmental and genetic factors, and lead to cell death.

Dr. Kuehn and colleagues evaluated if ER stress occurred in the trabecular meshwork of older adults, and if it occurred with a higher frequency in among patients with POAG.

An immunohistochemical evaluation was conducted using 30 human donor eyes with POAG and age-matched controls. The results showed that GADD153 and GRP78 were more frequently detected in the trabecular meshwork of eyes from older adults, and moderate or strong immunoreactivity was found in the majority of eyes from both glaucoma patients and controls.

However, the specimens with the most pronounced immunoreactivity tended to be derived from patients with POAG. Caspase-9 immunoreactivity was also observed less frequently than that for GADD178 or GRP78, and it was found to occur in cells from both patients and controls.

“ER stress in the trabecular meshwork per se is not a pathogenic response,” Dr. Kuehn said. “Some people may exhibit higher stress levels that could be damaging.”

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