Oxidative stress contributes to glaucomatous neuropathy

March 7, 2008

Oxidative stress is an early event in hydrostatic pressure/intraocular pressure-induced (IOP) neuronal damage.

Oxidative stress is an early event in hydrostatic pressure/intraocular pressure-induced (IOP) neuronal damage, according to a report published in the October 2007 issue of Investigative Ophthalmology & Visual Science.

Quan Liu from the University of California San Diego and colleagues from the University of Texas and Case Western Reserve University, USA and the University of Melbourne, Australia conducted a study to determine whether oxidative adduct formation or heme oxygenase-1 (HO-1) expression are altered in retinal ganglion cell cultures exposed to elevated hydrostatic pressure and in a mouse model of glaucoma.

Cultured RGC-5 cells were subjected to 0, 30, 60 or 100 mmHg hydrostatic pressure for two hours and the cells were harvested. Parallel experiments examined the recovery from this stress, the effect of direct 4-hydroxy-2-nonenal (HNE) treatment and the effect of pretreatment with resveratrol or quercetin. Mice were anaesthetized and IOP was increased to 30, 60 or 100 mmHg for one hour; the retinas were then harvested. HNE adduct formation and HO-1 expression were assessed by immunocytochemistry and immunoblotting.

The researchers discovered that increases of HNE-protein adducts (up to 5-fold) and HO-1 expression (up to 2.5-fold) in pressure-treated RGC-5 cells were dose dependent. During recovery experiments, HNE-protein adducts continued to increase for up to ten hours. In contrast, HO-1 expression decreased immediately. HNE, at concentrations as low as 5 µm, led to neurotoxicity in RGC-5 cells. HNE adducts and HO-1 expression increased in the mouse retina and optic nerve after acute IOP elevation up to 5.5- and 2-fold, respectively. Antioxidant treatment reduced the oxidative stress level in pressure-treated RGC-5 cells.

The results of this study support the view that oxidative damage contributes early to glaucomatous optic neuropathy.