Effect of hypercholesterolemia on inducible nitric oxide synthase expression in a rat model of elevated intraocular pressure

PURPOSE This study was performed to examine the effect of hypercholesterolemia on inducible nitric oxide synthase (NOS-2) expression and oxidative tissue injury in an experimental rat model of elevated IOP. METHODS Wistar rats were maintained on either regular chow or a high-cholesterol diet for 24 weeks. Intraocular pressure (IOP) was elevated in hypercholesterolemic rats by unilaterally cauterizing three episcleral vessels. Rats were divided into four experimental groups as follows; hypercholesterolemia, hypercholesterolemia+elevated IOP, elevated IOP and control. NOS-2 distribution, lipid peroxidation and retinal nerve fiber layer (RNFL) thickness was evaluated in all experimental groups at the end of 24 weeks. RESULTS Light microscopic evaluation of retinas in hypercholesterolemic rats revealed breaks and discontinuation in focal areas in the outer nuclear layer (ONL). NOS-2 positive staining was observed throughout the outer plexiform layer (OPL), inner plexiform layer (IPL) and ganglion cell layer (GCL) in rats with elevated IOP and/or hypercholesterolemia. Calculated values of RNFL thickness in hypercholesterolemic rats were significantly higher than those in the control and elevated IOP group. Vitreous malondialdehyde (MDA) levels detected in elevated IOP (3.51+/-0.31 nmol/mg protein) and hypercholesterolemia+elevated IOP (5.14+/-1.28 nmol/mg protein) groups were significantly higher than those detected in hypercholesterolemic (1.92+/-1.43 nmol/mg protein) and control (1.89+/-0.24 nmol/mg protein) groups. CONCLUSION The presented data confirms hypercholesterolemia as a risk factor in the development of glaucomatous optic neuropathy (GON) and suggests that increased circulating cholesterol may exacerbate disease progression by inducing NOS-2 expression and elevating oxidant tissue injury.