Erythropoietin Protects Retinal Pigment Epithelial Cells From Oxidative Damage

Chapterâ… Erythropoietin Protects Retinal Pigment Epithelial Cells from Oxidative DamageOxidative damage from reactive oxygen species(ROS) has been implicated in many diseases,including age-related macular degeneration,in which the retinal pigment epithelium(RPE) is considered a primary target.The aim of this study was to determine whether erythropoietin(EPO) protects cultured human RPE cells against oxidative damage and identify the pathways that may mediate protection.EPO (1 IU/mL) significantly increased the viability of oxidant-treated RPE cells;decreased the release of inflammatory cytokines,tumor necrosis factor-alpha and interleukin-1 beta;recovered the RPE cells barrier integrity disrupted by oxidative stress;prevented oxidant-induced cell DNA fragmentation and membrane phosphatidylserine exposure; and also reduced the levels of oxidant-induced intracellular ROS,restored cellular antioxidant potential,total antioxidant capacity,glutathione peroxidase,superoxide dismutase and decreased malondialdehyde,the end product of lipid peroxidation.EPO inhibited caspase-3 like activities.Protection by EPO was partly dependent on the activation of AKT1 and the maintenance of mitochondrial membrane potential.No enhanced or synergistic protection was observed during application of Z-DEVD-FMK (Caspase-3 inhibitor) combined with EPO as compared with cultures exposed to EPO and H₂O₂ alone.Together,the present work suggests that EPO could against oxidative injury induced cell death and mitochondrial dysfunction in RPE cells through modulation of AKT1 phosphorylation,mitochondrial membrane potential,and cysteine protease activity. Chapterâ…¡Elevated Erythropoietin in Vitreous of Patients with Rhegmatogenous Retinal Detachment and Proliferative VitreoretinopathyAim:To determine the vitreous Erythropoietin(EPO) level in patients with rhegmatogenous retinal detachment(RRD) and proliferative vitreoretinopathy(PVR).Methods:Levels of EPO in vitreous were measured using a sandwich ELISA kit from 64 patients,of whom 40 had RRD,13 had PVR and 11 had idiopathic macular hole(IMH) as control.Results:The mean level of EPO in RRD group(54.6±7.3 mU/ml) and PVR group(104.1±20.8 mU/ml) were significantly higher than that in IMH control group (14.4±3.6mU/ml;P<.001,P=.003,respectively).The mean EPO in PVR was higher than that in RRD,but the difference was not significant(P=.112).Conclusion:The vitreous EPO level was up-regulated in eyes with RRD and PVR. Chapterâ…¢Erythropoietin Is Increased in Aqueous Humor of Glaucomatous EyesObjective:To determine the aqueous concentration of EPO in patients with and without glaucoma.Study Design/ Patients and Methods:Prospective,comparative control study. Concentrations of EPO were measured using a sandwich ELISA kit in aqueous humor from 75 patients,of whom 55 had glaucoma(14 primary acute angle-closure glaucoma, PAACG;26 primary chronic angle-closure glaucoma,PCACG;11 primary open-angle glaucoma,POAG;4 neovascular glaucoma,NVG),and 20 had cataract only as control.Rseults:EPO concentrations in eyes with glaucoma(71.0±12.0 mU/mL) was significantly higher than that in eyes with cataract(6.4±0.8 mU/mL,P<0.001).There were no significant differences(P=0.421) between PCACG(28.84±3.9 mU/mL) and POAG(20.2±2.0 mU/mL),however,EPO concentrations in eyes with PAACG (118.5±14 mU/mL) were significantly higher than these two chronic subtypes of glaucoma(P<0.001,respectively).Unusually high EPO concentrations were detected in four eyes with NVG(319.5±47.7 mU/mL).No effect of age,gender,different eyes, body mass index of the aqueous humor EPO concentration could be detected(P>0.05). No significant correlation was found between aqueous humor and plasma EPO concentrations in PAACG and control group(P=0.285,0.500,respectively).Conculsion:Our Prospective study suggests that the aqueous humor EPO concentrations are increased in eyes with glaucoma.