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Background and Purpose: Retinal swelling, leading to irreversible visual impairment, is an important early complication in retinal ischemia/reperfusion (I/R) injury. Diosmin, a naturally occurring flavonoid glycoside, has been shown to have antioxidative and anti-inflammatory effects against I/R injury. The present study was performed to evaluate the retinal microvascular protective effect of diosmin in a model of I/R injury. Methods: Unilateral retinal I/R was induced by increasing intraocular pressure to 110 mm Hg for 60 min followed by reperfusion. Diosmin (100 mg/kg) or vehicle solution was administered intragastrically 30 min before the onset of ischemia and then daily after I/R injury until the animals were sacrificed. Rats were evaluated for retinal functional injury by electroretinogram (ERG) just before sacrifice. Retinas were harvested for HE staining, immunohistochemistry assay, ELISA, and western blotting analysis. Evans blue (EB) extravasation was determined to assess blood–retinal barrier (BRB) disruption and the structure of tight junctions (TJ) was examined by transmission electron microscopy. Results: Diosmin significantly ameliorated the reduction of b-wave, a-wave, and b/a ratio in ERG, alleviated retinal edema, protected the TJ structure, and reduced EB extravasation. All of these effects of diosmin were associated with increased zonular occluden-1 (ZO-1) and occludin protein expression and decreased VEGF/PEDF ratio. Conclusions: Maintenance of TJ integrity and reduced permeability of capillaries as well as improvements in retinal edema were observed with diosmin treatment, which may contribute to preservation of retinal function. This protective effect of diosmin may be at least partly attributed to its ability to regulate the VEGF/PEDF ratio. [ABSTRACT FROM AUTHOR]

Objective: Diosmin, a natural flavone glycoside, possesses antioxidant activity and has been used to alleviate ischemia/reperfusion (I/R) injury. The aim of this study was to clarify whether the administration of diosmin has a protective effect against I/R injury induced using the high intraocular pressure (IOP) model in rat retina, and to determine the possible antioxidant mechanisms involved. Methods: Retinal I/R injury was induced in the rats by elevating the IOP to 110 mmHg for 60 min. Diosmin (100 mg/kg) or vehicle solution was administered intragastrically 30 min before the onset of ischemia and then daily after I/R injury until the animals were sacrificed. The levels of malondialdehyde (MDA) and the activities of total-superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) in the retinal tissues were determined 24 h after I/R injury. At 7 days post-I/R injury, electroretinograms (ERGs) were recorded, and the density of surviving retinal ganglion cells (RGCs) was estimated by counting retrograde tracer-labeled cells in whole-mounted retinas. Retinal histological changes were also examined and quantified using light microscopy. Results: Diosmin significantly decreased the MDA levels and increased the activities of T-SOD, GSH-Px, and CAT in the retina of rats compared with the ischemia group ( P<0.05), and suppressed the I/R-induced reduction in the a- and b-wave amplitudes of the ERG ( P<0.05). The thickness of the entire retina, inner nuclear layer, inner plexiform layer, and outer retinal layer and the number of cells in the ganglion cell layer were significantly less after I/R injury ( P<0.05), and diosmin remarkably ameliorated these changes on retinal morphology. Diosmin also attenuated the I/R-induced loss of RGCs of the rat retina ( P<0.05). Conclusion: Diosmin protected the retina from I/R injury, possibly via a mechanism involving the regulation of oxidative parameters. [ABSTRACT FROM AUTHOR]

Purposes: To investigate whether valproic acid (VPA) has a neuroprotective effect against ischemia/reperfusion (I/R) injury in the rat retina, and to elucidate the potential antioxidant mechanisms involved. Methods: Adult male Wistar rats were randomly divided into four groups: sham (group A), sham plus VPA (group B), I/R plus vehicle (group C), and I/R plus VPA (group D). Retinal I/R injury was produced by inducing an exceedingly high intraocular pressure (IOP). Prior to insult, VPA was administered subcutaneously (300 mg/kg twice daily) for 7 days, after which the animal was sacrificed. Levels of retinal malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) were determined. Protein expressions of retinal poly(ADP-ribose) (PAR) and nitrotyrosine (NT) were analyzed by Western blotting 24 h after injury. Apoptosis of retinal cells was evaluated 24 h after I/R injury by immunofluorescence of activated caspase-3 in histological sections of retina. Seven days after reperfusion, electroretinography (ERG) was performed, and retinal histological changes were examined by light microscopy. Results: Following ischemia, the thickness of the entire retina, including the inner nuclear layer (INL) and inner plexiform layer (IPL), as well as the number of cells in the ganglion cell layer (GCL) were significantly greater in group D than in group C ( p < 0.05). VPA suppressed I/R-induced reductions in ERG a- and b-wave amplitudes ( p < 0.05). VPA attenuated I/R-induced activation of caspase-3 in ganglion cells and INL cells ( p < 0.001). VPA significantly decreased MDA levels and increased activities of SOD, GSH-Px, and CAT in group D ( p < 0.05). VPA attenuated activation of PAR and accumulation of NT in the retina after I/R ( p < 0.01). Conclusions: VPA protects the retina from I/R injury by enhancing anti-oxidative effects and inhibiting apoptosis of retinal cells. [ABSTRACT FROM AUTHOR]