Research For Retinal Iron Metabolism And Age Related Macular Degeneration

As ROS seduced by Fenton actions contributes to retinal pathological changes,oxidative stress involves in the pathogenesis of age-related macular degeneration, oneof the major threats to vision of senior population. On the other hand, iron overloadcould result in oxidative stress damage. Accordingly, abnormal iron metabolism viaseducing oxidative stress damage might engage in pathological progress ofage-related macular degeneration. As one important regulator for iron metabolism,hepcidin abides to degeneration of ferroportin once combined. Since ferroportin is theonly channel available for extracellular iron excretion, delicate regulation of hepcidinis of pivotal importance for maintaining steady intracellular iron level.This program is dedicated to exploring the regulation mechanism for hepcidin atlocal retinal tissue and protection role of deferiprone for iron-overloaded retina.To investigate the regulation mechanism of hepcidin, Bmp-6knocked-out mice,hepatic specific Bmp-6knocked-out mice and Venofer treated mice were introducedfor establishing. Mice of different month ages were adopted for evaluatingmorphological and biochemical indices via immunofluorescent scanning, real timePCR. According to experimental results, Bmp-6knocked-out mices excels inincreasing retinal iron level as ages accumulated in comparison with control group.Accordingly, since exempt from interference of bmp-6absence, expression ofhepcidin increased in parallel as iron level rose. In hepatic specific Bmp-6knocked-out mice, retinal iron level also increased as age accumulated, whichsurpassed its counterparts of control group. As iron administration continued, retinaliron overload was witnessed at RPE layer, yet changes of local hepcidin failed toantagonize changes of plasma iron level nor inhibit iron absorption. In summary, wereached the conclusion that hepcidin wield influence at local retinal tissue exemptfrom interference of Bmp6pathways. Iron level under circulation served as apowerful regulator for hepcidin.To explore the protection mechanism of DFP for retina, hepcidin knocked-outmice were executed12months after DFP administration and morphological and biochemical indices were analyzed via ERG, morphology and real-time PCR. Asshown in results, retinal damage was relative alleviated and more photoreceptor cellswere retrieved and degree of autonomous fatten fluorescence for RPE cells was alsomitigated under administration of DFP in comparison with control group. As revealedby molecular biological results, Rho/RPE65expression increased in comparison withcontrol group. Thus, DFP contributes to decreasing retinal iron levels and oxidativestress for protection of retina.